Melanoma

MONTREAL — Regression of a thin melanoma should not be the sole criterion to justify a sentinel lymph node biopsy, according to a retrospective study.

Regression alone is insufficient in the absence of other recognized high-risk predictors of sentinel lymph node (SLN) involvement, Dr. Pierre-Luc Dion said. More established risk factors include Breslow thickness greater than 1 mm, Clark level IV or V, and lesion ulceration.

Prognosis generally is better with thinner melanoma. Identification of the minority of thin melanoma patients who are at high risk for metastasis, however, remains a clinical challenge.

"There is an ongoing debate if regression is good news or bad news for patients. Some think it shows an immune response against tumor cells, but others say it can lead to an underestimation of the real thickness," Dr. Dion said at the annual conference of the Canadian Dermatology Association.

There is no consensus in the literature. One study of 65 thin melanomas with regression found that only 2 lesions (3%) had a positive SLN biopsy result (Ann. Surg. Oncol. 2003;10:558–61).

Another study found only 1 patient with a positive SLN biopsy among 344 who had thin melanomas (mean Breslow thickness of 1.1 mm) that had shown histologic regression (Ann. Surg. Oncol. 2008;15:316–22).

Other investigators have proposed that tumor regression predicts a higher risk of sentinel node involvement in thin melanomas (Br. J. Dermatol. 2003;149:662–3).

Dr. Dion and his colleagues assessed 693 patients treated at the melanoma clinics for Le Centre Hospitalier Universitaire de Québec-L'Hôtel-Dieu de Québec in Saint-Nicolas and Québec City. All of the patients underwent sentinel lymph node biopsy between 1996 and 2007. The median Breslow thickness was 2.28 mm and mean age was 55 years.

A total of 653 patients had a lesion that was greater than 1 mm. Their prognoses were compared with those of a group of 40 others with thinner melanoma and regression. Regression was determined by a pathologist, who found at least a 15% reduction in the lesion size on multiple slides.

Among the patients with regression, none had a positive lymph node, compared with 146 (22%) in the control group, suggesting regression alone is not a reliable predictor, said Dr. Dion of the hospital in Saint-Nicolas.

Of the 40 patients, 1 experienced complete regression. Another six patients in this group developed in situ melanoma. The median Breslow thickness among the remaining 33 patients was 0.6 mm. At a mean follow-up of almost 4 years, recurrence occurred in two patients, including one local recurrence and one transit metastasis, Dr. Dion said.

MONTREAL — Regression of a thin melanoma should not be the sole criterion to justify a sentinel lymph node biopsy, according to a retrospective study.

Regression alone is insufficient in the absence of other recognized high-risk predictors of sentinel lymph node (SLN) involvement, Dr. Pierre-Luc Dion said. More established risk factors include Breslow thickness greater than 1 mm, Clark level IV or V, and lesion ulceration.

Prognosis generally is better with thinner melanoma. Identification of the minority of thin melanoma patients who are at high risk for metastasis, however, remains a clinical challenge.

"There is an ongoing debate if regression is good news or bad news for patients. Some think it shows an immune response against tumor cells, but others say it can lead to an underestimation of the real thickness," Dr. Dion said at the annual conference of the Canadian Dermatology Association.

There is no consensus in the literature. One study of 65 thin melanomas with regression found that only 2 lesions (3%) had a positive SLN biopsy result (Ann. Surg. Oncol. 2003;10:558–61).

Another study found only 1 patient with a positive SLN biopsy among 344 who had thin melanomas (mean Breslow thickness of 1.1 mm) that had shown histologic regression (Ann. Surg. Oncol. 2008;15:316–22).

Other investigators have proposed that tumor regression predicts a higher risk of sentinel node involvement in thin melanomas (Br. J. Dermatol. 2003;149:662–3).

Dr. Dion and his colleagues assessed 693 patients treated at the melanoma clinics for Le Centre Hospitalier Universitaire de Québec-L'Hôtel-Dieu de Québec in Saint-Nicolas and Québec City. All of the patients underwent sentinel lymph node biopsy between 1996 and 2007. The median Breslow thickness was 2.28 mm and mean age was 55 years.

A total of 653 patients had a lesion that was greater than 1 mm. Their prognoses were compared with those of a group of 40 others with thinner melanoma and regression. Regression was determined by a pathologist, who found at least a 15% reduction in the lesion size on multiple slides.

Among the patients with regression, none had a positive lymph node, compared with 146 (22%) in the control group, suggesting regression alone is not a reliable predictor, said Dr. Dion of the hospital in Saint-Nicolas.

Of the 40 patients, 1 experienced complete regression. Another six patients in this group developed in situ melanoma. The median Breslow thickness among the remaining 33 patients was 0.6 mm. At a mean follow-up of almost 4 years, recurrence occurred in two patients, including one local recurrence and one transit metastasis, Dr. Dion said.

MONTREAL — Regression of a thin melanoma should not be the sole criterion to justify a sentinel lymph node biopsy, according to a retrospective study.

Regression alone is insufficient in the absence of other recognized high-risk predictors of sentinel lymph node (SLN) involvement, Dr. Pierre-Luc Dion said. More established risk factors include Breslow thickness greater than 1 mm, Clark level IV or V, and lesion ulceration.

Prognosis generally is better with thinner melanoma. Identification of the minority of thin melanoma patients who are at high risk for metastasis, however, remains a clinical challenge.

"There is an ongoing debate if regression is good news or bad news for patients. Some think it shows an immune response against tumor cells, but others say it can lead to an underestimation of the real thickness," Dr. Dion said at the annual conference of the Canadian Dermatology Association.

There is no consensus in the literature. One study of 65 thin melanomas with regression found that only 2 lesions (3%) had a positive SLN biopsy result (Ann. Surg. Oncol. 2003;10:558–61).

Another study found only 1 patient with a positive SLN biopsy among 344 who had thin melanomas (mean Breslow thickness of 1.1 mm) that had shown histologic regression (Ann. Surg. Oncol. 2008;15:316–22).

Other investigators have proposed that tumor regression predicts a higher risk of sentinel node involvement in thin melanomas (Br. J. Dermatol. 2003;149:662–3).

Dr. Dion and his colleagues assessed 693 patients treated at the melanoma clinics for Le Centre Hospitalier Universitaire de Québec-L'Hôtel-Dieu de Québec in Saint-Nicolas and Québec City. All of the patients underwent sentinel lymph node biopsy between 1996 and 2007. The median Breslow thickness was 2.28 mm and mean age was 55 years.

A total of 653 patients had a lesion that was greater than 1 mm. Their prognoses were compared with those of a group of 40 others with thinner melanoma and regression. Regression was determined by a pathologist, who found at least a 15% reduction in the lesion size on multiple slides.

Among the patients with regression, none had a positive lymph node, compared with 146 (22%) in the control group, suggesting regression alone is not a reliable predictor, said Dr. Dion of the hospital in Saint-Nicolas.

Of the 40 patients, 1 experienced complete regression. Another six patients in this group developed in situ melanoma. The median Breslow thickness among the remaining 33 patients was 0.6 mm. At a mean follow-up of almost 4 years, recurrence occurred in two patients, including one local recurrence and one transit metastasis, Dr. Dion said.

KYOTO, JAPAN — Intratumoral interferon-gamma gene therapy delivered via an adenoviral vector induces systemic as well as local immune responses in patients with primary cutaneous T- or B-cell lymphoma, reported Dr. Mirjana Urosevic reported.

This novel approach to interferon-gamma gene transfer using an intralesionally injected adenoviral vector showed impressive safety and tolerability as well as promising efficacy in a multicenter combined phase I/II clinical trial, according to Dr. Urosevic of the University of Zürich.

Recombinant interferon-alfa and -gamma therapy have demonstrated efficacy in primary cutaneous lymphomas. However, it is accompanied by severe systemic toxicity, she said at an international investigative dermatology meeting.

Dr. Urosevic and her coworkers believe that placing substantial quantities of the interferon-gamma gene within a tumor will result in production of sustained high levels of the cytokine by the patient's own cells without systemic toxicity.

Incorporating the interferon-gamma gene into an adenoviral vector offers a substantial bonus, she said: The vector itself appears to have therapeutic efficacy. The nonreplicating recombinant adenovirus Dr. Urosevic and her colleagues are using, known as TG1042, activates interferon-alfa genes, resulting in increased intralesional expression of interferon-alfa, supplementing the tumor-rejecting effects of the transgene-induced interferon-gamma.

She reported on 33 evaluable patients who received the investigational gene therapy at six centers in Switzerland, Germany, and France in an open-label clinical trial. Twenty-eight had cutaneous T-cell lymphoma and five had cutaneous B-cell lymphoma. All had advanced disease and previously had failed to respond to at least two first-line forms of therapy.

The injected tumors showed a partial response in 10 patients and a complete response in 9 others, for an overall 57% local clinical response rate. Half of the cutaneous T-cell lymphoma patients had a local therapeutic response, as did, notably, all five with cutaneous B-cell lymphomas, she said.

Fourteen patients experienced global responses, with regression of untreated as well as treated lesions. Seven of these patients had complete responses, while the rest demonstrated partial responses.

The treatment regimen consisted of once-weekly intratumoral injection of 3×1011 viral particles for 3 weeks, then a 2-week break, followed by a patient evaluation. If the patient was stable or had at least a partial response, then treatment resumed; if the disease progressed, treatment stopped. These three-injection cycles were repeated for up to 12 cycles, or 36 injections, Dr. Urosevic reported at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

All patients have mounted neutralizing antiadenovirus antibodies in response to the vector. However, these antibodies have not blocked the interferon response to the gene transfer or the vector itself, she said.

The study was sponsored by Transgene of Strasbourg, France.

KYOTO, JAPAN — Intratumoral interferon-gamma gene therapy delivered via an adenoviral vector induces systemic as well as local immune responses in patients with primary cutaneous T- or B-cell lymphoma, reported Dr. Mirjana Urosevic reported.

This novel approach to interferon-gamma gene transfer using an intralesionally injected adenoviral vector showed impressive safety and tolerability as well as promising efficacy in a multicenter combined phase I/II clinical trial, according to Dr. Urosevic of the University of Zürich.

Recombinant interferon-alfa and -gamma therapy have demonstrated efficacy in primary cutaneous lymphomas. However, it is accompanied by severe systemic toxicity, she said at an international investigative dermatology meeting.

Dr. Urosevic and her coworkers believe that placing substantial quantities of the interferon-gamma gene within a tumor will result in production of sustained high levels of the cytokine by the patient's own cells without systemic toxicity.

Incorporating the interferon-gamma gene into an adenoviral vector offers a substantial bonus, she said: The vector itself appears to have therapeutic efficacy. The nonreplicating recombinant adenovirus Dr. Urosevic and her colleagues are using, known as TG1042, activates interferon-alfa genes, resulting in increased intralesional expression of interferon-alfa, supplementing the tumor-rejecting effects of the transgene-induced interferon-gamma.

She reported on 33 evaluable patients who received the investigational gene therapy at six centers in Switzerland, Germany, and France in an open-label clinical trial. Twenty-eight had cutaneous T-cell lymphoma and five had cutaneous B-cell lymphoma. All had advanced disease and previously had failed to respond to at least two first-line forms of therapy.

The injected tumors showed a partial response in 10 patients and a complete response in 9 others, for an overall 57% local clinical response rate. Half of the cutaneous T-cell lymphoma patients had a local therapeutic response, as did, notably, all five with cutaneous B-cell lymphomas, she said.

Fourteen patients experienced global responses, with regression of untreated as well as treated lesions. Seven of these patients had complete responses, while the rest demonstrated partial responses.

The treatment regimen consisted of once-weekly intratumoral injection of 3×1011 viral particles for 3 weeks, then a 2-week break, followed by a patient evaluation. If the patient was stable or had at least a partial response, then treatment resumed; if the disease progressed, treatment stopped. These three-injection cycles were repeated for up to 12 cycles, or 36 injections, Dr. Urosevic reported at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

All patients have mounted neutralizing antiadenovirus antibodies in response to the vector. However, these antibodies have not blocked the interferon response to the gene transfer or the vector itself, she said.

The study was sponsored by Transgene of Strasbourg, France.

KYOTO, JAPAN — Intratumoral interferon-gamma gene therapy delivered via an adenoviral vector induces systemic as well as local immune responses in patients with primary cutaneous T- or B-cell lymphoma, reported Dr. Mirjana Urosevic reported.

This novel approach to interferon-gamma gene transfer using an intralesionally injected adenoviral vector showed impressive safety and tolerability as well as promising efficacy in a multicenter combined phase I/II clinical trial, according to Dr. Urosevic of the University of Zürich.

Recombinant interferon-alfa and -gamma therapy have demonstrated efficacy in primary cutaneous lymphomas. However, it is accompanied by severe systemic toxicity, she said at an international investigative dermatology meeting.

Dr. Urosevic and her coworkers believe that placing substantial quantities of the interferon-gamma gene within a tumor will result in production of sustained high levels of the cytokine by the patient's own cells without systemic toxicity.

Incorporating the interferon-gamma gene into an adenoviral vector offers a substantial bonus, she said: The vector itself appears to have therapeutic efficacy. The nonreplicating recombinant adenovirus Dr. Urosevic and her colleagues are using, known as TG1042, activates interferon-alfa genes, resulting in increased intralesional expression of interferon-alfa, supplementing the tumor-rejecting effects of the transgene-induced interferon-gamma.

She reported on 33 evaluable patients who received the investigational gene therapy at six centers in Switzerland, Germany, and France in an open-label clinical trial. Twenty-eight had cutaneous T-cell lymphoma and five had cutaneous B-cell lymphoma. All had advanced disease and previously had failed to respond to at least two first-line forms of therapy.

The injected tumors showed a partial response in 10 patients and a complete response in 9 others, for an overall 57% local clinical response rate. Half of the cutaneous T-cell lymphoma patients had a local therapeutic response, as did, notably, all five with cutaneous B-cell lymphomas, she said.

Fourteen patients experienced global responses, with regression of untreated as well as treated lesions. Seven of these patients had complete responses, while the rest demonstrated partial responses.

The treatment regimen consisted of once-weekly intratumoral injection of 3×1011 viral particles for 3 weeks, then a 2-week break, followed by a patient evaluation. If the patient was stable or had at least a partial response, then treatment resumed; if the disease progressed, treatment stopped. These three-injection cycles were repeated for up to 12 cycles, or 36 injections, Dr. Urosevic reported at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

All patients have mounted neutralizing antiadenovirus antibodies in response to the vector. However, these antibodies have not blocked the interferon response to the gene transfer or the vector itself, she said.

The study was sponsored by Transgene of Strasbourg, France.

VANCOUVER — Compared with the lidocaine concentration typically used for local anesthesia during Mohs surgery, a lower concentration achieved equivalent pain relief with a 53% reduction in the total dose administered in a randomized, double-blind trial of 149 patients.

"We found in our clinic that 10%-15% of our patients were actually exceeding the recommended lidocaine dose of 7 mg/kg when we used 1% lidocaine with 1:100,000 epinephrine, which is the most common concentration of lidocaine used for Mohs surgery," explained Pamela Morganroth, noting that the patients nonetheless did not experience any symptoms.

"These patients often have large tumors, multiple sites, and extensive reconstructions," she said at the annual meeting of the American College of Mohs Surgery.

Minimizing lidocaine dose is important because symptoms of lidocaine toxicity occur in a dose-dependent manner; moreover, exceeding the recommended limit—even if symptoms do not occur or occur as a result of other conditions—exposes surgeons to medicolegal risk, observed Ms. Morganroth, a medical student at the University of Pennsylvania, Philadelphia.

"Unfortunately, multiple factors influence lidocaine dose," including older age; pregnancy; and renal, cardiac, and hepatic impairment, she added, "so it's virtually impossible to set a uniform maximum recommended lidocaine dose."

In the study, patients undergoing Mohs surgery were randomly assigned to local anesthesia consisting of 1.0% lidocaine with 1:100,000 epinephrine or 0.5% lidocaine with 1:200,000 epinephrine. Surgery was performed by a single physician who was unaware of the patient's assignment. The surgical field was infiltrated immediately before each Mohs layer and the reconstruction, with use of local infiltration and field blocks instead of regional nerve blocks. Excision began as soon as the patient reported no pain to a pinprick stimulus.

Outcomes included the total lidocaine dose administered (including all stages of Mohs surgery and the reconstruction) and patient comfort, which was measured subjectively with a 100-mm visual analog scale and objectively according to the volume of "rescue" lidocaine administered during the surgery. Analyses were based on 74 patients (with 83 tumors) in the 1.0% lidocaine group and 75 patients (with 85 tumors) in the 0.5% lidocaine group.

The mean total dose of lidocaine administered to patients in the 0.5% group was significantly lower, by 53%, than that administered to patients in the 1.0% group (139 mg vs. 297 mg). Mean scores for patient-rated pain (3.88 vs. 3.11 mm, respectively) or mean volume of rescue lidocaine administered (0.85 vs. 0.33 cc) did not differ significantly, Ms. Morganroth reported.

It appears that "0.5% lidocaine provides equivalent patient comfort at half the total dose of lidocaine as compared to 1.0% lidocaine," she said, while also acknowledging that the study did not measure blood levels of the drug.

"Our study demonstrates that 0.5% lidocaine decreases the risk of dose-dependent lidocaine toxicity without compromising patient comfort during Mohs surgery," said Ms. Morganroth, who reported having no conflicts of interest.

VANCOUVER — Compared with the lidocaine concentration typically used for local anesthesia during Mohs surgery, a lower concentration achieved equivalent pain relief with a 53% reduction in the total dose administered in a randomized, double-blind trial of 149 patients.

"We found in our clinic that 10%-15% of our patients were actually exceeding the recommended lidocaine dose of 7 mg/kg when we used 1% lidocaine with 1:100,000 epinephrine, which is the most common concentration of lidocaine used for Mohs surgery," explained Pamela Morganroth, noting that the patients nonetheless did not experience any symptoms.

"These patients often have large tumors, multiple sites, and extensive reconstructions," she said at the annual meeting of the American College of Mohs Surgery.

Minimizing lidocaine dose is important because symptoms of lidocaine toxicity occur in a dose-dependent manner; moreover, exceeding the recommended limit—even if symptoms do not occur or occur as a result of other conditions—exposes surgeons to medicolegal risk, observed Ms. Morganroth, a medical student at the University of Pennsylvania, Philadelphia.

"Unfortunately, multiple factors influence lidocaine dose," including older age; pregnancy; and renal, cardiac, and hepatic impairment, she added, "so it's virtually impossible to set a uniform maximum recommended lidocaine dose."

In the study, patients undergoing Mohs surgery were randomly assigned to local anesthesia consisting of 1.0% lidocaine with 1:100,000 epinephrine or 0.5% lidocaine with 1:200,000 epinephrine. Surgery was performed by a single physician who was unaware of the patient's assignment. The surgical field was infiltrated immediately before each Mohs layer and the reconstruction, with use of local infiltration and field blocks instead of regional nerve blocks. Excision began as soon as the patient reported no pain to a pinprick stimulus.

Outcomes included the total lidocaine dose administered (including all stages of Mohs surgery and the reconstruction) and patient comfort, which was measured subjectively with a 100-mm visual analog scale and objectively according to the volume of "rescue" lidocaine administered during the surgery. Analyses were based on 74 patients (with 83 tumors) in the 1.0% lidocaine group and 75 patients (with 85 tumors) in the 0.5% lidocaine group.

The mean total dose of lidocaine administered to patients in the 0.5% group was significantly lower, by 53%, than that administered to patients in the 1.0% group (139 mg vs. 297 mg). Mean scores for patient-rated pain (3.88 vs. 3.11 mm, respectively) or mean volume of rescue lidocaine administered (0.85 vs. 0.33 cc) did not differ significantly, Ms. Morganroth reported.

It appears that "0.5% lidocaine provides equivalent patient comfort at half the total dose of lidocaine as compared to 1.0% lidocaine," she said, while also acknowledging that the study did not measure blood levels of the drug.

"Our study demonstrates that 0.5% lidocaine decreases the risk of dose-dependent lidocaine toxicity without compromising patient comfort during Mohs surgery," said Ms. Morganroth, who reported having no conflicts of interest.

VANCOUVER — Compared with the lidocaine concentration typically used for local anesthesia during Mohs surgery, a lower concentration achieved equivalent pain relief with a 53% reduction in the total dose administered in a randomized, double-blind trial of 149 patients.

"We found in our clinic that 10%-15% of our patients were actually exceeding the recommended lidocaine dose of 7 mg/kg when we used 1% lidocaine with 1:100,000 epinephrine, which is the most common concentration of lidocaine used for Mohs surgery," explained Pamela Morganroth, noting that the patients nonetheless did not experience any symptoms.

"These patients often have large tumors, multiple sites, and extensive reconstructions," she said at the annual meeting of the American College of Mohs Surgery.

Minimizing lidocaine dose is important because symptoms of lidocaine toxicity occur in a dose-dependent manner; moreover, exceeding the recommended limit—even if symptoms do not occur or occur as a result of other conditions—exposes surgeons to medicolegal risk, observed Ms. Morganroth, a medical student at the University of Pennsylvania, Philadelphia.

"Unfortunately, multiple factors influence lidocaine dose," including older age; pregnancy; and renal, cardiac, and hepatic impairment, she added, "so it's virtually impossible to set a uniform maximum recommended lidocaine dose."

In the study, patients undergoing Mohs surgery were randomly assigned to local anesthesia consisting of 1.0% lidocaine with 1:100,000 epinephrine or 0.5% lidocaine with 1:200,000 epinephrine. Surgery was performed by a single physician who was unaware of the patient's assignment. The surgical field was infiltrated immediately before each Mohs layer and the reconstruction, with use of local infiltration and field blocks instead of regional nerve blocks. Excision began as soon as the patient reported no pain to a pinprick stimulus.

Outcomes included the total lidocaine dose administered (including all stages of Mohs surgery and the reconstruction) and patient comfort, which was measured subjectively with a 100-mm visual analog scale and objectively according to the volume of "rescue" lidocaine administered during the surgery. Analyses were based on 74 patients (with 83 tumors) in the 1.0% lidocaine group and 75 patients (with 85 tumors) in the 0.5% lidocaine group.

The mean total dose of lidocaine administered to patients in the 0.5% group was significantly lower, by 53%, than that administered to patients in the 1.0% group (139 mg vs. 297 mg). Mean scores for patient-rated pain (3.88 vs. 3.11 mm, respectively) or mean volume of rescue lidocaine administered (0.85 vs. 0.33 cc) did not differ significantly, Ms. Morganroth reported.

It appears that "0.5% lidocaine provides equivalent patient comfort at half the total dose of lidocaine as compared to 1.0% lidocaine," she said, while also acknowledging that the study did not measure blood levels of the drug.

"Our study demonstrates that 0.5% lidocaine decreases the risk of dose-dependent lidocaine toxicity without compromising patient comfort during Mohs surgery," said Ms. Morganroth, who reported having no conflicts of interest.

WILLIAMSBURG, VA. — Imiquimod can be a powerful tool for fighting in situ squamous cell carcinomas and superficial basal cell carcinomas, Dr. Roger Ceilley said.

"A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas," said Dr. Ceilley, at the annual meeting of the American Society for Mohs Surgery. "We may worry that when treating carcinoma in situ topically, that we are just treating the tip of the iceberg, but there are a few studies now that show even patients with an early invasive squamous cell carcinoma [SCC] treated three times a week for 12 weeks show clearing of the deeper component of the lesion."

Evidence is mounting for imiquimod's use on various sites of SCC in situ, including lesions on the anterior leg and penis, said Dr. Ceilley, a professor of dermatology at the University of Iowa, Iowa City. He noted seven case reports of imiquimod used successfully to treat penile lesions. The cream was applied anywhere from twice a week to every other day, depending on individual tolerance, for 8-16 weeks. "This is clearly an off-label use and you wouldn't want to do it without consulting a urologist but, with close management, this might be an alternative for an SCC that would otherwise result in a penectomy," he said.

Combined with 5-fluorouracil, imiquimod is especially effective for SCC lesions on the scalp, and dorsum of the hand—places that are often resistant to either treatment alone.

The cream also is approved for use in superficial basal cell carcinoma, where it has shown effectiveness. A 2004 placebo-controlled study found that up to 82% of patients had histologic clearance after a 6-week treatment cycle (J. Am. Acad. Dermatol. 2004;50:722-33). The study also found no significant difference in clearance rates among patients who used the cream five or seven times a week, lending support for the shorter treatment time. However, clearance was highly correlated with increased severity of erythema, erosion, and scabbing or crusting. The cosmetic outcomes were excellent.

For BCC, Dr. Ceilley said he prefers to use imiquimod prior to Mohs surgery, in conjunction with aggressive curettage and electrodesiccation. Treating for a few weeks preoperatively can reduce the defect, decrease the frequency of residual tumor, and improve cosmetic appearance.

"You can really define the lesions more carefully, minimizing the area of surgery you have to do," he said.

Evidence is mounting for the use of imiquimod in nodular BCC as well—especially in smaller, low-risk lesions or as adjunctive therapy. The original 2002 dosing study found a histologic clearance rate of up to 76%, with no significant difference between those who applied the medication daily for 12 or 16 weeks (Arch. Dermatol. 2002;138:1165-71), said Dr. Ceilley.

A more recent study found that while 70 of 90 patients (78%) had a complete clinical response, there was clinically visible tumor still present in 20 patients (22%). There was complete histopathologic clearance observed in 58 patients (64%), while residual tumor remained in 32 patients (36%). Efficacy was better in lesions smaller than 1 cm in diameter. The authors concluded that, since 17% of patients in the study with clinical clearance still had pathologic evidence of disease, excisional biopsy of the treated site is still indicated (J. Am. Acad. Dermatol. 2007;57:616-21).

Dr. Ceilley stated that he did not have any conflicts of interest to disclose.

'A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas.' DR. CEILLEY

WILLIAMSBURG, VA. — Imiquimod can be a powerful tool for fighting in situ squamous cell carcinomas and superficial basal cell carcinomas, Dr. Roger Ceilley said.

"A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas," said Dr. Ceilley, at the annual meeting of the American Society for Mohs Surgery. "We may worry that when treating carcinoma in situ topically, that we are just treating the tip of the iceberg, but there are a few studies now that show even patients with an early invasive squamous cell carcinoma [SCC] treated three times a week for 12 weeks show clearing of the deeper component of the lesion."

Evidence is mounting for imiquimod's use on various sites of SCC in situ, including lesions on the anterior leg and penis, said Dr. Ceilley, a professor of dermatology at the University of Iowa, Iowa City. He noted seven case reports of imiquimod used successfully to treat penile lesions. The cream was applied anywhere from twice a week to every other day, depending on individual tolerance, for 8-16 weeks. "This is clearly an off-label use and you wouldn't want to do it without consulting a urologist but, with close management, this might be an alternative for an SCC that would otherwise result in a penectomy," he said.

Combined with 5-fluorouracil, imiquimod is especially effective for SCC lesions on the scalp, and dorsum of the hand—places that are often resistant to either treatment alone.

The cream also is approved for use in superficial basal cell carcinoma, where it has shown effectiveness. A 2004 placebo-controlled study found that up to 82% of patients had histologic clearance after a 6-week treatment cycle (J. Am. Acad. Dermatol. 2004;50:722-33). The study also found no significant difference in clearance rates among patients who used the cream five or seven times a week, lending support for the shorter treatment time. However, clearance was highly correlated with increased severity of erythema, erosion, and scabbing or crusting. The cosmetic outcomes were excellent.

For BCC, Dr. Ceilley said he prefers to use imiquimod prior to Mohs surgery, in conjunction with aggressive curettage and electrodesiccation. Treating for a few weeks preoperatively can reduce the defect, decrease the frequency of residual tumor, and improve cosmetic appearance.

"You can really define the lesions more carefully, minimizing the area of surgery you have to do," he said.

Evidence is mounting for the use of imiquimod in nodular BCC as well—especially in smaller, low-risk lesions or as adjunctive therapy. The original 2002 dosing study found a histologic clearance rate of up to 76%, with no significant difference between those who applied the medication daily for 12 or 16 weeks (Arch. Dermatol. 2002;138:1165-71), said Dr. Ceilley.

A more recent study found that while 70 of 90 patients (78%) had a complete clinical response, there was clinically visible tumor still present in 20 patients (22%). There was complete histopathologic clearance observed in 58 patients (64%), while residual tumor remained in 32 patients (36%). Efficacy was better in lesions smaller than 1 cm in diameter. The authors concluded that, since 17% of patients in the study with clinical clearance still had pathologic evidence of disease, excisional biopsy of the treated site is still indicated (J. Am. Acad. Dermatol. 2007;57:616-21).

Dr. Ceilley stated that he did not have any conflicts of interest to disclose.

'A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas.' DR. CEILLEY

WILLIAMSBURG, VA. — Imiquimod can be a powerful tool for fighting in situ squamous cell carcinomas and superficial basal cell carcinomas, Dr. Roger Ceilley said.

"A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas," said Dr. Ceilley, at the annual meeting of the American Society for Mohs Surgery. "We may worry that when treating carcinoma in situ topically, that we are just treating the tip of the iceberg, but there are a few studies now that show even patients with an early invasive squamous cell carcinoma [SCC] treated three times a week for 12 weeks show clearing of the deeper component of the lesion."

Evidence is mounting for imiquimod's use on various sites of SCC in situ, including lesions on the anterior leg and penis, said Dr. Ceilley, a professor of dermatology at the University of Iowa, Iowa City. He noted seven case reports of imiquimod used successfully to treat penile lesions. The cream was applied anywhere from twice a week to every other day, depending on individual tolerance, for 8-16 weeks. "This is clearly an off-label use and you wouldn't want to do it without consulting a urologist but, with close management, this might be an alternative for an SCC that would otherwise result in a penectomy," he said.

Combined with 5-fluorouracil, imiquimod is especially effective for SCC lesions on the scalp, and dorsum of the hand—places that are often resistant to either treatment alone.

The cream also is approved for use in superficial basal cell carcinoma, where it has shown effectiveness. A 2004 placebo-controlled study found that up to 82% of patients had histologic clearance after a 6-week treatment cycle (J. Am. Acad. Dermatol. 2004;50:722-33). The study also found no significant difference in clearance rates among patients who used the cream five or seven times a week, lending support for the shorter treatment time. However, clearance was highly correlated with increased severity of erythema, erosion, and scabbing or crusting. The cosmetic outcomes were excellent.

For BCC, Dr. Ceilley said he prefers to use imiquimod prior to Mohs surgery, in conjunction with aggressive curettage and electrodesiccation. Treating for a few weeks preoperatively can reduce the defect, decrease the frequency of residual tumor, and improve cosmetic appearance.

"You can really define the lesions more carefully, minimizing the area of surgery you have to do," he said.

Evidence is mounting for the use of imiquimod in nodular BCC as well—especially in smaller, low-risk lesions or as adjunctive therapy. The original 2002 dosing study found a histologic clearance rate of up to 76%, with no significant difference between those who applied the medication daily for 12 or 16 weeks (Arch. Dermatol. 2002;138:1165-71), said Dr. Ceilley.

A more recent study found that while 70 of 90 patients (78%) had a complete clinical response, there was clinically visible tumor still present in 20 patients (22%). There was complete histopathologic clearance observed in 58 patients (64%), while residual tumor remained in 32 patients (36%). Efficacy was better in lesions smaller than 1 cm in diameter. The authors concluded that, since 17% of patients in the study with clinical clearance still had pathologic evidence of disease, excisional biopsy of the treated site is still indicated (J. Am. Acad. Dermatol. 2007;57:616-21).

Dr. Ceilley stated that he did not have any conflicts of interest to disclose.

'A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas.' DR. CEILLEY

KYOTO, JAPAN — Topical calcineurin inhibitors should be used with caution when a diagnosis of atopic dermatitis is less than certain because they might accelerate progression of early-stage mycosis fungoides, often clinically indistinguishable from the atopic disorder.

"Biopsies should be obtained before using them on infiltrated facial lesions, which could be folliculotropic mycosis fungoides," Grace C. Sun advised at an international investigative dermatology meeting.

Because both the symptoms and skin biopsy findings are often nonspecific in early mycosis fungoides, many affected patients are misdiagnosed as having other skin diseases—particularly atopic dermatitis—for years before the proper diagnosis is eventually made. To examine the impact of topical calcineurin inhibitor (TCI) therapy in such patients, Ms. Sun of the M.D. Anderson Cancer Center, Houston, and coworkers conducted a retrospective study of 414 M.D. Anderson patients diagnosed with stage 1A or 1B mycosis fungoides during 2001-2007.

Of the 414 patients, 27 progressed beyond their initial T1/T2 skin stage within 6 years. In a multivariate regression analysis controlling for potential confounders, three factors emerged as being independently associated with reduced time to progression: the presence of large cell transformation on skin biopsy, which conferred a 3.3-fold increased risk of progression; prior pimecrolimus use, carrying a 5.4-fold increased risk; and a high serum lactate dehydrogenase concentration, which boosted the risk of early progression 23-fold.

Twenty-one of the 414 patients had a history of pimecrolimus therapy; 4 of those 21 progressed within 6 years. So did 1 of 10 patients who had been on tacrolimus and 18 of 250 with a history of topical corticosteroid therapy prior to being diagnosed with mycosis fungoides.

Of the four patients with a history of pimecrolimus use who progressed to a more advanced T stage within 6 years after diagnosis of mycosis fungoides, three had skin biopsies consistent with folliculotropic mycosis fungoides, a more aggressive variant. Three of the four patients developed tumors in areas where they had earlier applied pimecrolimus: on the head and face in two patients with folliculotropic mycosis fungoides, and on the antecubital fossa and hands in another patient.

The number of individuals with a history of tacrolimus therapy was too small to draw any conclusions regarding a possible relationship with time to progression, said Ms. Sun.

Seventeen percent of the 414 patients reported being initially misdiagnosed as having eczema. Six of these 69 patients progressed within 6 years, but none had previously used a TCI, she reported at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Both of the available TCIs—tacrolimus and pimecrolimus—are immunosuppressive, she said. The use of oral tacrolimus to prevent graft rejection in transplant recipients has been associated with increased risk of lymphoma; in animal models, systemic administration of either TCI has been found to increase the risk of lymphoma.

KYOTO, JAPAN — Topical calcineurin inhibitors should be used with caution when a diagnosis of atopic dermatitis is less than certain because they might accelerate progression of early-stage mycosis fungoides, often clinically indistinguishable from the atopic disorder.

"Biopsies should be obtained before using them on infiltrated facial lesions, which could be folliculotropic mycosis fungoides," Grace C. Sun advised at an international investigative dermatology meeting.

Because both the symptoms and skin biopsy findings are often nonspecific in early mycosis fungoides, many affected patients are misdiagnosed as having other skin diseases—particularly atopic dermatitis—for years before the proper diagnosis is eventually made. To examine the impact of topical calcineurin inhibitor (TCI) therapy in such patients, Ms. Sun of the M.D. Anderson Cancer Center, Houston, and coworkers conducted a retrospective study of 414 M.D. Anderson patients diagnosed with stage 1A or 1B mycosis fungoides during 2001-2007.

Of the 414 patients, 27 progressed beyond their initial T1/T2 skin stage within 6 years. In a multivariate regression analysis controlling for potential confounders, three factors emerged as being independently associated with reduced time to progression: the presence of large cell transformation on skin biopsy, which conferred a 3.3-fold increased risk of progression; prior pimecrolimus use, carrying a 5.4-fold increased risk; and a high serum lactate dehydrogenase concentration, which boosted the risk of early progression 23-fold.

Twenty-one of the 414 patients had a history of pimecrolimus therapy; 4 of those 21 progressed within 6 years. So did 1 of 10 patients who had been on tacrolimus and 18 of 250 with a history of topical corticosteroid therapy prior to being diagnosed with mycosis fungoides.

Of the four patients with a history of pimecrolimus use who progressed to a more advanced T stage within 6 years after diagnosis of mycosis fungoides, three had skin biopsies consistent with folliculotropic mycosis fungoides, a more aggressive variant. Three of the four patients developed tumors in areas where they had earlier applied pimecrolimus: on the head and face in two patients with folliculotropic mycosis fungoides, and on the antecubital fossa and hands in another patient.

The number of individuals with a history of tacrolimus therapy was too small to draw any conclusions regarding a possible relationship with time to progression, said Ms. Sun.

Seventeen percent of the 414 patients reported being initially misdiagnosed as having eczema. Six of these 69 patients progressed within 6 years, but none had previously used a TCI, she reported at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Both of the available TCIs—tacrolimus and pimecrolimus—are immunosuppressive, she said. The use of oral tacrolimus to prevent graft rejection in transplant recipients has been associated with increased risk of lymphoma; in animal models, systemic administration of either TCI has been found to increase the risk of lymphoma.

KYOTO, JAPAN — Topical calcineurin inhibitors should be used with caution when a diagnosis of atopic dermatitis is less than certain because they might accelerate progression of early-stage mycosis fungoides, often clinically indistinguishable from the atopic disorder.

"Biopsies should be obtained before using them on infiltrated facial lesions, which could be folliculotropic mycosis fungoides," Grace C. Sun advised at an international investigative dermatology meeting.

Because both the symptoms and skin biopsy findings are often nonspecific in early mycosis fungoides, many affected patients are misdiagnosed as having other skin diseases—particularly atopic dermatitis—for years before the proper diagnosis is eventually made. To examine the impact of topical calcineurin inhibitor (TCI) therapy in such patients, Ms. Sun of the M.D. Anderson Cancer Center, Houston, and coworkers conducted a retrospective study of 414 M.D. Anderson patients diagnosed with stage 1A or 1B mycosis fungoides during 2001-2007.

Of the 414 patients, 27 progressed beyond their initial T1/T2 skin stage within 6 years. In a multivariate regression analysis controlling for potential confounders, three factors emerged as being independently associated with reduced time to progression: the presence of large cell transformation on skin biopsy, which conferred a 3.3-fold increased risk of progression; prior pimecrolimus use, carrying a 5.4-fold increased risk; and a high serum lactate dehydrogenase concentration, which boosted the risk of early progression 23-fold.

Twenty-one of the 414 patients had a history of pimecrolimus therapy; 4 of those 21 progressed within 6 years. So did 1 of 10 patients who had been on tacrolimus and 18 of 250 with a history of topical corticosteroid therapy prior to being diagnosed with mycosis fungoides.

Of the four patients with a history of pimecrolimus use who progressed to a more advanced T stage within 6 years after diagnosis of mycosis fungoides, three had skin biopsies consistent with folliculotropic mycosis fungoides, a more aggressive variant. Three of the four patients developed tumors in areas where they had earlier applied pimecrolimus: on the head and face in two patients with folliculotropic mycosis fungoides, and on the antecubital fossa and hands in another patient.

The number of individuals with a history of tacrolimus therapy was too small to draw any conclusions regarding a possible relationship with time to progression, said Ms. Sun.

Seventeen percent of the 414 patients reported being initially misdiagnosed as having eczema. Six of these 69 patients progressed within 6 years, but none had previously used a TCI, she reported at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Both of the available TCIs—tacrolimus and pimecrolimus—are immunosuppressive, she said. The use of oral tacrolimus to prevent graft rejection in transplant recipients has been associated with increased risk of lymphoma; in animal models, systemic administration of either TCI has been found to increase the risk of lymphoma.

The Skin Cancer Foundation's brochure entitled "The ABCDEs of Melanoma" is now available in both English and Spanish. The foldout helps patients to identify the most important differences between common moles and melanomas: Asymmetry, Border irregularity, Color variations, and large Diameter and Evolving. To order copies, contact the foundation at 800-754-6490.

The Skin Cancer Foundation's brochure entitled "The ABCDEs of Melanoma" is now available in both English and Spanish. The foldout helps patients to identify the most important differences between common moles and melanomas: Asymmetry, Border irregularity, Color variations, and large Diameter and Evolving. To order copies, contact the foundation at 800-754-6490.

The Skin Cancer Foundation's brochure entitled "The ABCDEs of Melanoma" is now available in both English and Spanish. The foldout helps patients to identify the most important differences between common moles and melanomas: Asymmetry, Border irregularity, Color variations, and large Diameter and Evolving. To order copies, contact the foundation at 800-754-6490.

Prolonged therapy with pegylated interferon has been found to improve recurrence-free survival in patients with excised stage III melanoma in a randomized phase III trial.

In contrast, survival free of distant metastases was numerically but not statistically significantly better with adjuvant pegylated interferon, and the treatment had no apparent effect on overall survival, Dr. Alexander M. M. Eggermont and his associates reported in the European Organisation for Research and Treatment of Cancer (EORTC) trial 18991 (Lancet 2008;372:117-26).

In an editorial comment that accompanied the report, Dr. Vernon K. Sondak and Dr. Lawrence E. Flaherty wrote that "many patients with melanoma are willing to accept significant toxicity in exchange for a modest improvement in recurrence-free survival, even in the absence of an overall survival effect," (Lancet 2008;372:89-90).

It remains to be seen, however, whether such patients and their physicians will accept 5 years of pegylated interferon treatment "for an absolute benefit in recurrence-free survival of about 6% at 4 years," they noted.

Dr. Eggermont and his colleagues compared the therapy with observation alone in a randomized controlled trial involving 1,256 patients treated at 99 medical centers in 17 countries. All patients had undergone complete excision of stage III melanoma and complete regional lymphadenectomy.

The study was funded by Schering-Plough Research International.

The two study groups were well matched according to disease substage, number of involved lymph nodes, thickness of the primary tumor, and ulceration of the primary tumor. Patients who took interferon received high-dose induction therapy for 8 weeks, followed by once-weekly self-administered subcutaneous injections for an intended duration of 5 years, said Dr. Eggermont, of Erasmus University, Rotterdam, the Netherlands, and his associates.

After a median of 4 years of follow-up, significantly fewer recurrences had developed in the interferon group than in the observation group, with a 6.7% absolute difference in estimated rates of recurrence-free survival. The therapy's benefit was seen early in the course of treatment and remained at a consistent level throughout the study, the investigators said.

However, there was no difference in overall survival between patients who took pegylated interferon and those who did not.

The drug was most effective in patients who had microscopic rather than palpable nodal disease, patients whose involvement was limited to one lymph node, and in patients with ulcerated rather than nonulcerated tumors. These groups accounted for approximately 40% of the treated patients.

One-third of the study subjects who took interferon discontinued the drug because of toxicity. The most common adverse effects were fatigue and depression, which were reported in 25% and 16% of patients, respectively. Anorexia, liver function abnormalities, myalgia, headache, nausea, and fever also were reported.

In their editorial comment, Dr. Sondak of H. Lee Moffitt Cancer Center, Tampa, and Dr. Flaherty of Karmanos Cancer Institute, Detroit, said that a 4-year follow-up "is too short for final conclusions." Further follow-up and more clinical trials are needed. However, they added, "for the large group of patients with melanoma found in their sentinel node, we believe this regimen will be an attractive alternative to high-dose interferon."

Dr. Eggermont, Dr. Sondak, and Dr. Flaherty have all been paid consultants for Schering-Plough.

Prolonged therapy with pegylated interferon has been found to improve recurrence-free survival in patients with excised stage III melanoma in a randomized phase III trial.

In contrast, survival free of distant metastases was numerically but not statistically significantly better with adjuvant pegylated interferon, and the treatment had no apparent effect on overall survival, Dr. Alexander M. M. Eggermont and his associates reported in the European Organisation for Research and Treatment of Cancer (EORTC) trial 18991 (Lancet 2008;372:117-26).

In an editorial comment that accompanied the report, Dr. Vernon K. Sondak and Dr. Lawrence E. Flaherty wrote that "many patients with melanoma are willing to accept significant toxicity in exchange for a modest improvement in recurrence-free survival, even in the absence of an overall survival effect," (Lancet 2008;372:89-90).

It remains to be seen, however, whether such patients and their physicians will accept 5 years of pegylated interferon treatment "for an absolute benefit in recurrence-free survival of about 6% at 4 years," they noted.

Dr. Eggermont and his colleagues compared the therapy with observation alone in a randomized controlled trial involving 1,256 patients treated at 99 medical centers in 17 countries. All patients had undergone complete excision of stage III melanoma and complete regional lymphadenectomy.

The study was funded by Schering-Plough Research International.

The two study groups were well matched according to disease substage, number of involved lymph nodes, thickness of the primary tumor, and ulceration of the primary tumor. Patients who took interferon received high-dose induction therapy for 8 weeks, followed by once-weekly self-administered subcutaneous injections for an intended duration of 5 years, said Dr. Eggermont, of Erasmus University, Rotterdam, the Netherlands, and his associates.

After a median of 4 years of follow-up, significantly fewer recurrences had developed in the interferon group than in the observation group, with a 6.7% absolute difference in estimated rates of recurrence-free survival. The therapy's benefit was seen early in the course of treatment and remained at a consistent level throughout the study, the investigators said.

However, there was no difference in overall survival between patients who took pegylated interferon and those who did not.

The drug was most effective in patients who had microscopic rather than palpable nodal disease, patients whose involvement was limited to one lymph node, and in patients with ulcerated rather than nonulcerated tumors. These groups accounted for approximately 40% of the treated patients.

One-third of the study subjects who took interferon discontinued the drug because of toxicity. The most common adverse effects were fatigue and depression, which were reported in 25% and 16% of patients, respectively. Anorexia, liver function abnormalities, myalgia, headache, nausea, and fever also were reported.

In their editorial comment, Dr. Sondak of H. Lee Moffitt Cancer Center, Tampa, and Dr. Flaherty of Karmanos Cancer Institute, Detroit, said that a 4-year follow-up "is too short for final conclusions." Further follow-up and more clinical trials are needed. However, they added, "for the large group of patients with melanoma found in their sentinel node, we believe this regimen will be an attractive alternative to high-dose interferon."

Dr. Eggermont, Dr. Sondak, and Dr. Flaherty have all been paid consultants for Schering-Plough.

Prolonged therapy with pegylated interferon has been found to improve recurrence-free survival in patients with excised stage III melanoma in a randomized phase III trial.

In contrast, survival free of distant metastases was numerically but not statistically significantly better with adjuvant pegylated interferon, and the treatment had no apparent effect on overall survival, Dr. Alexander M. M. Eggermont and his associates reported in the European Organisation for Research and Treatment of Cancer (EORTC) trial 18991 (Lancet 2008;372:117-26).

In an editorial comment that accompanied the report, Dr. Vernon K. Sondak and Dr. Lawrence E. Flaherty wrote that "many patients with melanoma are willing to accept significant toxicity in exchange for a modest improvement in recurrence-free survival, even in the absence of an overall survival effect," (Lancet 2008;372:89-90).

It remains to be seen, however, whether such patients and their physicians will accept 5 years of pegylated interferon treatment "for an absolute benefit in recurrence-free survival of about 6% at 4 years," they noted.

Dr. Eggermont and his colleagues compared the therapy with observation alone in a randomized controlled trial involving 1,256 patients treated at 99 medical centers in 17 countries. All patients had undergone complete excision of stage III melanoma and complete regional lymphadenectomy.

The study was funded by Schering-Plough Research International.

The two study groups were well matched according to disease substage, number of involved lymph nodes, thickness of the primary tumor, and ulceration of the primary tumor. Patients who took interferon received high-dose induction therapy for 8 weeks, followed by once-weekly self-administered subcutaneous injections for an intended duration of 5 years, said Dr. Eggermont, of Erasmus University, Rotterdam, the Netherlands, and his associates.

After a median of 4 years of follow-up, significantly fewer recurrences had developed in the interferon group than in the observation group, with a 6.7% absolute difference in estimated rates of recurrence-free survival. The therapy's benefit was seen early in the course of treatment and remained at a consistent level throughout the study, the investigators said.

However, there was no difference in overall survival between patients who took pegylated interferon and those who did not.

The drug was most effective in patients who had microscopic rather than palpable nodal disease, patients whose involvement was limited to one lymph node, and in patients with ulcerated rather than nonulcerated tumors. These groups accounted for approximately 40% of the treated patients.

One-third of the study subjects who took interferon discontinued the drug because of toxicity. The most common adverse effects were fatigue and depression, which were reported in 25% and 16% of patients, respectively. Anorexia, liver function abnormalities, myalgia, headache, nausea, and fever also were reported.

In their editorial comment, Dr. Sondak of H. Lee Moffitt Cancer Center, Tampa, and Dr. Flaherty of Karmanos Cancer Institute, Detroit, said that a 4-year follow-up "is too short for final conclusions." Further follow-up and more clinical trials are needed. However, they added, "for the large group of patients with melanoma found in their sentinel node, we believe this regimen will be an attractive alternative to high-dose interferon."

Dr. Eggermont, Dr. Sondak, and Dr. Flaherty have all been paid consultants for Schering-Plough.

CHICAGO — Cetuximab can be added safely and apparently to good effect when giving a standard induction regimen to patients with newly diagnosed, locally advanced head and neck cancer, reported investigators at the annual meeting of the American Society of Clinical Oncology.

In a phase I study looking at the addition of cetuximab (Erbitux) to induction chemotherapy with docetaxel (Taxotere), cisplatin, and 5-fluorouracil (the TPF regimen), 14 of 19 treated patients had a complete clinical response, 5 had a partial clinical response, and all 19 had a partial radiographic response, reported Dr. Robert I. Haddad, who is a clinical investigator in the Head and Neck Cancer Center at the Dana Farber Cancer Institute in Boston.

"The preliminary efficacy data [are] encouraging in this patient population with fairly advanced presentation," Dr. Haddad said.

The TPF regimen is both a new standard for induction chemotherapy in patients with previously untreated squamous cell carcinomas of the head and neck, and a platform for testing new agents such as cetuximab, which has been shown to have efficacy in head and neck cancer as a single agent and in combination with radiation therapy and cistplatin/5-fluorouracil (PF) chemotherapy, Dr. Haddad said.

He and his colleagues conducted a phase I study of the maximum tolerated dose of 5-fluorouracil (5-FU) in the TPF regimen when cetuximab was added. Secondary goals of the study included a toxicity assessment and response rates.

They enrolled 28 patients with biopsy-proven squamous cell carcinoma of the head and neck, with primary tumor sites in the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx. Patients with unknown primary site squamous cell carcinomas were also eligible.

The patients had to have stage III or IV disease with no evidence of distant metastases, and they had to have no prior chemotherapy, radiation therapy, or surgery, measurable disease by RECIST (Response Evaluation Criteria in Solid Tumors). In addition, patients needed to have good Eastern Cooperative Oncology Group performance status (0 or 1), and normal hematologic, renal, and liver function.

Patients received 400 mg/m

The treatment plan called for three cycles of induction chemotherapy, with TPF every 21 days, plus weekly cetuximab in doses of 250 mg/m

At the end of induction, restaging was performed and then patients underwent definitive chemoradiotherapy with a platinum-based regimen according to the institution's standard.

One of the patients withdrew consent before toxicity could be assessed, leaving 27 available for the analysis. Of these patients, 19 had completed chemoradiotherapy at the time Dr. Haddad presented the data.

There were no dose-limiting toxicities after the first cycle of cetuximab/TPF with 5-FU at 750 or 850 mg/m

But in that expanded cohort, there were two cases of gastrointestinal bleeding and one of febrile neutropenia, causing the investigators to reconsider 5-FU dosing, and they instead settled on 850 mg as the maximum tolerated dose. Of the 10 patients planned for enrollment in the expanded cohort at this dose, nine had enrolled at the time of the analysis. Only one dose-limiting toxicity was reported: mucositis.

Among the 12 patients in total enrolled at the 850-mg dose (3 from the original cohort, plus 9 additionally enrolled), there were four cases of grade 4 neutropenia and one of grade 4 diarrhea. Grade 3 events include three cases of neutropenia, two of febrile neutropenia, one mucositis (dose limiting), one fatigue, and one syncope. Skin toxicities included acneiform rash (seven grade 2 and one grade 3), and four cases of grade 2 nail fissuring and/or paronychial infection.

At the time of the data presentation, 19 of 27 patients had completed chemoradiotherapy with a platinum-based agent, and 8 remained on treatment. All but one of the patients received 70-Gy radiation over 7 weeks; the remaining patients received 59 Gy over 10 weeks.

An analysis of the best overall response showed a clinical complete response in 14 patients, and partial response in 5. Radiographic evaluation at the end of induction but before radiation showed a partial response in all 19 patients.

"All of these patients had still-persistent abnormalities on CT or PET," Dr. Haddad said. "Keep in mind these patients have fairly advanced nodal presentations, and often the CT scan or imaging is not normalized for these patients."

Among the 13 patients who underwent primary site biopsy after induction, 11 had pathologic complete response, and 2 had a partial response.

All patients were alive at 6-month follow-up; one patient with a stage T4 N2b cancer of the base of the tongue had local/regional recurrence and is currently on palliative chemotherapy. Two patients had neck dissections performed after chemoradiotherapy, and neither had pathologic evidence of residual cancer in the surgical specimen.

A randomized multicenter phase II study is being planned to compare the cetuximab and TPF combination with the M.D. Anderson Cancer Center induction regimen consisting of carboplatin, paclitaxel, and cetiuximab, Dr. Haddad said.

The study was supported by Bristol-Myers Squibb. Dr. Haddad disclosed receiving honoraria and research support from the company, and honoraria from Sanofi-Aventis and Imclone Systems.

CHICAGO — Cetuximab can be added safely and apparently to good effect when giving a standard induction regimen to patients with newly diagnosed, locally advanced head and neck cancer, reported investigators at the annual meeting of the American Society of Clinical Oncology.

In a phase I study looking at the addition of cetuximab (Erbitux) to induction chemotherapy with docetaxel (Taxotere), cisplatin, and 5-fluorouracil (the TPF regimen), 14 of 19 treated patients had a complete clinical response, 5 had a partial clinical response, and all 19 had a partial radiographic response, reported Dr. Robert I. Haddad, who is a clinical investigator in the Head and Neck Cancer Center at the Dana Farber Cancer Institute in Boston.

"The preliminary efficacy data [are] encouraging in this patient population with fairly advanced presentation," Dr. Haddad said.

The TPF regimen is both a new standard for induction chemotherapy in patients with previously untreated squamous cell carcinomas of the head and neck, and a platform for testing new agents such as cetuximab, which has been shown to have efficacy in head and neck cancer as a single agent and in combination with radiation therapy and cistplatin/5-fluorouracil (PF) chemotherapy, Dr. Haddad said.

He and his colleagues conducted a phase I study of the maximum tolerated dose of 5-fluorouracil (5-FU) in the TPF regimen when cetuximab was added. Secondary goals of the study included a toxicity assessment and response rates.

They enrolled 28 patients with biopsy-proven squamous cell carcinoma of the head and neck, with primary tumor sites in the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx. Patients with unknown primary site squamous cell carcinomas were also eligible.

The patients had to have stage III or IV disease with no evidence of distant metastases, and they had to have no prior chemotherapy, radiation therapy, or surgery, measurable disease by RECIST (Response Evaluation Criteria in Solid Tumors). In addition, patients needed to have good Eastern Cooperative Oncology Group performance status (0 or 1), and normal hematologic, renal, and liver function.

Patients received 400 mg/m

The treatment plan called for three cycles of induction chemotherapy, with TPF every 21 days, plus weekly cetuximab in doses of 250 mg/m

At the end of induction, restaging was performed and then patients underwent definitive chemoradiotherapy with a platinum-based regimen according to the institution's standard.

One of the patients withdrew consent before toxicity could be assessed, leaving 27 available for the analysis. Of these patients, 19 had completed chemoradiotherapy at the time Dr. Haddad presented the data.

There were no dose-limiting toxicities after the first cycle of cetuximab/TPF with 5-FU at 750 or 850 mg/m

But in that expanded cohort, there were two cases of gastrointestinal bleeding and one of febrile neutropenia, causing the investigators to reconsider 5-FU dosing, and they instead settled on 850 mg as the maximum tolerated dose. Of the 10 patients planned for enrollment in the expanded cohort at this dose, nine had enrolled at the time of the analysis. Only one dose-limiting toxicity was reported: mucositis.

Among the 12 patients in total enrolled at the 850-mg dose (3 from the original cohort, plus 9 additionally enrolled), there were four cases of grade 4 neutropenia and one of grade 4 diarrhea. Grade 3 events include three cases of neutropenia, two of febrile neutropenia, one mucositis (dose limiting), one fatigue, and one syncope. Skin toxicities included acneiform rash (seven grade 2 and one grade 3), and four cases of grade 2 nail fissuring and/or paronychial infection.

At the time of the data presentation, 19 of 27 patients had completed chemoradiotherapy with a platinum-based agent, and 8 remained on treatment. All but one of the patients received 70-Gy radiation over 7 weeks; the remaining patients received 59 Gy over 10 weeks.

An analysis of the best overall response showed a clinical complete response in 14 patients, and partial response in 5. Radiographic evaluation at the end of induction but before radiation showed a partial response in all 19 patients.

"All of these patients had still-persistent abnormalities on CT or PET," Dr. Haddad said. "Keep in mind these patients have fairly advanced nodal presentations, and often the CT scan or imaging is not normalized for these patients."

Among the 13 patients who underwent primary site biopsy after induction, 11 had pathologic complete response, and 2 had a partial response.

All patients were alive at 6-month follow-up; one patient with a stage T4 N2b cancer of the base of the tongue had local/regional recurrence and is currently on palliative chemotherapy. Two patients had neck dissections performed after chemoradiotherapy, and neither had pathologic evidence of residual cancer in the surgical specimen.

A randomized multicenter phase II study is being planned to compare the cetuximab and TPF combination with the M.D. Anderson Cancer Center induction regimen consisting of carboplatin, paclitaxel, and cetiuximab, Dr. Haddad said.

The study was supported by Bristol-Myers Squibb. Dr. Haddad disclosed receiving honoraria and research support from the company, and honoraria from Sanofi-Aventis and Imclone Systems.

CHICAGO — Cetuximab can be added safely and apparently to good effect when giving a standard induction regimen to patients with newly diagnosed, locally advanced head and neck cancer, reported investigators at the annual meeting of the American Society of Clinical Oncology.

In a phase I study looking at the addition of cetuximab (Erbitux) to induction chemotherapy with docetaxel (Taxotere), cisplatin, and 5-fluorouracil (the TPF regimen), 14 of 19 treated patients had a complete clinical response, 5 had a partial clinical response, and all 19 had a partial radiographic response, reported Dr. Robert I. Haddad, who is a clinical investigator in the Head and Neck Cancer Center at the Dana Farber Cancer Institute in Boston.

"The preliminary efficacy data [are] encouraging in this patient population with fairly advanced presentation," Dr. Haddad said.

The TPF regimen is both a new standard for induction chemotherapy in patients with previously untreated squamous cell carcinomas of the head and neck, and a platform for testing new agents such as cetuximab, which has been shown to have efficacy in head and neck cancer as a single agent and in combination with radiation therapy and cistplatin/5-fluorouracil (PF) chemotherapy, Dr. Haddad said.

He and his colleagues conducted a phase I study of the maximum tolerated dose of 5-fluorouracil (5-FU) in the TPF regimen when cetuximab was added. Secondary goals of the study included a toxicity assessment and response rates.

They enrolled 28 patients with biopsy-proven squamous cell carcinoma of the head and neck, with primary tumor sites in the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx. Patients with unknown primary site squamous cell carcinomas were also eligible.

The patients had to have stage III or IV disease with no evidence of distant metastases, and they had to have no prior chemotherapy, radiation therapy, or surgery, measurable disease by RECIST (Response Evaluation Criteria in Solid Tumors). In addition, patients needed to have good Eastern Cooperative Oncology Group performance status (0 or 1), and normal hematologic, renal, and liver function.

Patients received 400 mg/m

The treatment plan called for three cycles of induction chemotherapy, with TPF every 21 days, plus weekly cetuximab in doses of 250 mg/m

At the end of induction, restaging was performed and then patients underwent definitive chemoradiotherapy with a platinum-based regimen according to the institution's standard.

One of the patients withdrew consent before toxicity could be assessed, leaving 27 available for the analysis. Of these patients, 19 had completed chemoradiotherapy at the time Dr. Haddad presented the data.

There were no dose-limiting toxicities after the first cycle of cetuximab/TPF with 5-FU at 750 or 850 mg/m

But in that expanded cohort, there were two cases of gastrointestinal bleeding and one of febrile neutropenia, causing the investigators to reconsider 5-FU dosing, and they instead settled on 850 mg as the maximum tolerated dose. Of the 10 patients planned for enrollment in the expanded cohort at this dose, nine had enrolled at the time of the analysis. Only one dose-limiting toxicity was reported: mucositis.

Among the 12 patients in total enrolled at the 850-mg dose (3 from the original cohort, plus 9 additionally enrolled), there were four cases of grade 4 neutropenia and one of grade 4 diarrhea. Grade 3 events include three cases of neutropenia, two of febrile neutropenia, one mucositis (dose limiting), one fatigue, and one syncope. Skin toxicities included acneiform rash (seven grade 2 and one grade 3), and four cases of grade 2 nail fissuring and/or paronychial infection.

At the time of the data presentation, 19 of 27 patients had completed chemoradiotherapy with a platinum-based agent, and 8 remained on treatment. All but one of the patients received 70-Gy radiation over 7 weeks; the remaining patients received 59 Gy over 10 weeks.

An analysis of the best overall response showed a clinical complete response in 14 patients, and partial response in 5. Radiographic evaluation at the end of induction but before radiation showed a partial response in all 19 patients.

"All of these patients had still-persistent abnormalities on CT or PET," Dr. Haddad said. "Keep in mind these patients have fairly advanced nodal presentations, and often the CT scan or imaging is not normalized for these patients."

Among the 13 patients who underwent primary site biopsy after induction, 11 had pathologic complete response, and 2 had a partial response.

All patients were alive at 6-month follow-up; one patient with a stage T4 N2b cancer of the base of the tongue had local/regional recurrence and is currently on palliative chemotherapy. Two patients had neck dissections performed after chemoradiotherapy, and neither had pathologic evidence of residual cancer in the surgical specimen.

A randomized multicenter phase II study is being planned to compare the cetuximab and TPF combination with the M.D. Anderson Cancer Center induction regimen consisting of carboplatin, paclitaxel, and cetiuximab, Dr. Haddad said.

The study was supported by Bristol-Myers Squibb. Dr. Haddad disclosed receiving honoraria and research support from the company, and honoraria from Sanofi-Aventis and Imclone Systems.

KYOTO, JAPAN — Prophylactic oral N-acetylcysteine has shown early promise as a novel melanoma chemoprevention strategy, said Dr. Douglas Grossman.

Taking N-acetylcysteine (NAC) episodically in anticipation of a day at the beach or before other heavy sun exposure may prevent UV-induced oxidative damage to melanocytic nevi, thereby reducing the long-term risk of malignant transformation, explained Dr. Grossman at an international investigative dermatology meeting.

The drug targets oxidative damage, a specific oncogenic pathway that is induced by UV irradiation. NAC has the ability to sidestep the inherent drawbacks of daily chemopreventive therapy, including compliance problems and drug side effects, said Dr. Grossman of the University of Utah, Salt Lake City. And sunscreens alone seem inadequate for melanoma prevention; in fact, some studies have shown a higher incidence of melanoma in sunscreen users, he said.

NAC is an ideal drug to study for chemoprevention. It has a relatively short serum half-life of 5.5 hours. It is rapidly metabolized to cysteine and converted to glutathione, a potent antioxidant that is depleted by UV.

"NAC is well characterized, cheap, cell-permeable, and has a safety record already demonstrated in humans," the dermatologist noted.

Other investigators have already shown that NAC is useful in preventing oxidative damage in the skin. It is FDA approved for the treatment of toxicity from acute acetaminophen overdose. More recently, it has been used to prevent intravenous contrast-induced nephropathy.

In mouse studies, Dr. Grossman and coworkers have demonstrated that NAC prevents UV-induced formation of the carcinogen 8-oxoguanine and delays onset of UV-induced melanoma (Clin. Cancer Res. 2007;13:5952-8).

In Kyoto, he presented the first clinical study of NAC for melanoma chemoprevention. It involved eight patients who underwent biopsy of a nevus prior to administration of a single 1,200-mg oral dose of NAC. Three hours after NAC administration, a second nevus was removed. The nevi were then irradiated ex vivo with UV at 4,000 J/m

When the nevi were analyzed 24 hours post UV exposure, the control samples showed roughly a 50% reduction in glutathione levels and an increase in 8-oxoguanine, compared with baseline. In contrast, the nevi exposed in vivo to NAC showed no depletion of glutathione and no rise in 8-oxoguanine in three of eight patients.

In hindsight, Dr. Grossman said, the analysis probably should have been done 48 hours post UV exposure rather than at 24 hours. The earlier mouse studies suggested oxidative stress and damage were at their maximum levels at the 48-hour time point.

"We see this as a pilot study in which we had some moderate success in a small number of patients. We're now poised to do a second trial using the 48-hour time point, which we think will be much more robust," Dr. Grossman said at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Also planned are clinical trials looking at NAC's protective effect in response to UV irradiation in vivo. The possibility that NAC is protective when taken following UV exposure is also worthy of investigation, he added.

The optimal dose of NAC for chemoprevention remains unknown. The 1,200-mg dose used in this study was well tolerated. "Higher doses are probably safe, but we don't know if they'd confer greater protection or not, so we'll probably stick with 1,200 mg," said Dr. Grossman.

His study was funded by the university's Huntsman Cancer Institute.

KYOTO, JAPAN — Prophylactic oral N-acetylcysteine has shown early promise as a novel melanoma chemoprevention strategy, said Dr. Douglas Grossman.

Taking N-acetylcysteine (NAC) episodically in anticipation of a day at the beach or before other heavy sun exposure may prevent UV-induced oxidative damage to melanocytic nevi, thereby reducing the long-term risk of malignant transformation, explained Dr. Grossman at an international investigative dermatology meeting.

The drug targets oxidative damage, a specific oncogenic pathway that is induced by UV irradiation. NAC has the ability to sidestep the inherent drawbacks of daily chemopreventive therapy, including compliance problems and drug side effects, said Dr. Grossman of the University of Utah, Salt Lake City. And sunscreens alone seem inadequate for melanoma prevention; in fact, some studies have shown a higher incidence of melanoma in sunscreen users, he said.

NAC is an ideal drug to study for chemoprevention. It has a relatively short serum half-life of 5.5 hours. It is rapidly metabolized to cysteine and converted to glutathione, a potent antioxidant that is depleted by UV.

"NAC is well characterized, cheap, cell-permeable, and has a safety record already demonstrated in humans," the dermatologist noted.

Other investigators have already shown that NAC is useful in preventing oxidative damage in the skin. It is FDA approved for the treatment of toxicity from acute acetaminophen overdose. More recently, it has been used to prevent intravenous contrast-induced nephropathy.

In mouse studies, Dr. Grossman and coworkers have demonstrated that NAC prevents UV-induced formation of the carcinogen 8-oxoguanine and delays onset of UV-induced melanoma (Clin. Cancer Res. 2007;13:5952-8).

In Kyoto, he presented the first clinical study of NAC for melanoma chemoprevention. It involved eight patients who underwent biopsy of a nevus prior to administration of a single 1,200-mg oral dose of NAC. Three hours after NAC administration, a second nevus was removed. The nevi were then irradiated ex vivo with UV at 4,000 J/m

When the nevi were analyzed 24 hours post UV exposure, the control samples showed roughly a 50% reduction in glutathione levels and an increase in 8-oxoguanine, compared with baseline. In contrast, the nevi exposed in vivo to NAC showed no depletion of glutathione and no rise in 8-oxoguanine in three of eight patients.

In hindsight, Dr. Grossman said, the analysis probably should have been done 48 hours post UV exposure rather than at 24 hours. The earlier mouse studies suggested oxidative stress and damage were at their maximum levels at the 48-hour time point.

"We see this as a pilot study in which we had some moderate success in a small number of patients. We're now poised to do a second trial using the 48-hour time point, which we think will be much more robust," Dr. Grossman said at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Also planned are clinical trials looking at NAC's protective effect in response to UV irradiation in vivo. The possibility that NAC is protective when taken following UV exposure is also worthy of investigation, he added.

The optimal dose of NAC for chemoprevention remains unknown. The 1,200-mg dose used in this study was well tolerated. "Higher doses are probably safe, but we don't know if they'd confer greater protection or not, so we'll probably stick with 1,200 mg," said Dr. Grossman.

His study was funded by the university's Huntsman Cancer Institute.

KYOTO, JAPAN — Prophylactic oral N-acetylcysteine has shown early promise as a novel melanoma chemoprevention strategy, said Dr. Douglas Grossman.

Taking N-acetylcysteine (NAC) episodically in anticipation of a day at the beach or before other heavy sun exposure may prevent UV-induced oxidative damage to melanocytic nevi, thereby reducing the long-term risk of malignant transformation, explained Dr. Grossman at an international investigative dermatology meeting.

The drug targets oxidative damage, a specific oncogenic pathway that is induced by UV irradiation. NAC has the ability to sidestep the inherent drawbacks of daily chemopreventive therapy, including compliance problems and drug side effects, said Dr. Grossman of the University of Utah, Salt Lake City. And sunscreens alone seem inadequate for melanoma prevention; in fact, some studies have shown a higher incidence of melanoma in sunscreen users, he said.

NAC is an ideal drug to study for chemoprevention. It has a relatively short serum half-life of 5.5 hours. It is rapidly metabolized to cysteine and converted to glutathione, a potent antioxidant that is depleted by UV.

"NAC is well characterized, cheap, cell-permeable, and has a safety record already demonstrated in humans," the dermatologist noted.

Other investigators have already shown that NAC is useful in preventing oxidative damage in the skin. It is FDA approved for the treatment of toxicity from acute acetaminophen overdose. More recently, it has been used to prevent intravenous contrast-induced nephropathy.

In mouse studies, Dr. Grossman and coworkers have demonstrated that NAC prevents UV-induced formation of the carcinogen 8-oxoguanine and delays onset of UV-induced melanoma (Clin. Cancer Res. 2007;13:5952-8).

In Kyoto, he presented the first clinical study of NAC for melanoma chemoprevention. It involved eight patients who underwent biopsy of a nevus prior to administration of a single 1,200-mg oral dose of NAC. Three hours after NAC administration, a second nevus was removed. The nevi were then irradiated ex vivo with UV at 4,000 J/m

When the nevi were analyzed 24 hours post UV exposure, the control samples showed roughly a 50% reduction in glutathione levels and an increase in 8-oxoguanine, compared with baseline. In contrast, the nevi exposed in vivo to NAC showed no depletion of glutathione and no rise in 8-oxoguanine in three of eight patients.

In hindsight, Dr. Grossman said, the analysis probably should have been done 48 hours post UV exposure rather than at 24 hours. The earlier mouse studies suggested oxidative stress and damage were at their maximum levels at the 48-hour time point.

"We see this as a pilot study in which we had some moderate success in a small number of patients. We're now poised to do a second trial using the 48-hour time point, which we think will be much more robust," Dr. Grossman said at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Also planned are clinical trials looking at NAC's protective effect in response to UV irradiation in vivo. The possibility that NAC is protective when taken following UV exposure is also worthy of investigation, he added.

The optimal dose of NAC for chemoprevention remains unknown. The 1,200-mg dose used in this study was well tolerated. "Higher doses are probably safe, but we don't know if they'd confer greater protection or not, so we'll probably stick with 1,200 mg," said Dr. Grossman.

His study was funded by the university's Huntsman Cancer Institute.

CHICAGO — Single nucleotide polymorphisms in DNA repair genes may help predict not only metastatic capacity but also survival in patients with primary cutaneous melanoma, according to a 400-patient study presented as a poster at the annual meeting of the American Society of Clinical Oncology.

Dr. Dirk Schadendorf of the skin cancer unit of the German Cancer Research Center in Heidelberg, Germany, and his coauthors genotyped 13 single-nucleotide polymorphisms (SNPs) from eight different DNA repair genes in 400 cutaneous melanoma patients. Average patient follow-up was 3.7 years, with 46% of patients having metastasis during that period.

The researchers found that melanoma patients with the AA genotype for the R399Q XRCC1 polymorphism showed better overall survival (hazard ratio, 0.32; P = .03) and metastasis-free survival (HR, 0.40; P = .007) compared with patients who were heterozygous and homozygous (GG). However, survival following metastasis was comparable between the groups.

The study also found that patients with AG and GG genotypes for the −1842 XRCC3 polymorphism (1843bp 5′ of the start codon in the promoter region) showed decreased survival following metastasis, although these differences in mortality after metastasis were significant only for the AG genotype (HR, 1.99; P = .003 [for AG]; HR, 1.53; P = .5 [for GG]) as was mortality overall (HR, 1.68; P = .02 for AG), compared with patients who were homozygous (AA). Metastasis-free survival did not differ between the groups.

No association was found for the other nine SNPs.

"Genetic stability, at least during a specific phase of tumor development, appears to be necessary for a malignant melanoma cell to give rise to metastasis. Accordingly, impaired repair functionality could account for reduced metastatic capacity, better metastasis-free survival, and overall survival as observed in patients homozygous for the variant allele for the R399Q XRCC1 and the K751Q ERCC2 polymorphisms in our study," the researchers wrote.

"Our data support the concept that overall survival is a sum of factors influencing time from diagnosis of the primary [cancer] to first relapse and factors contributing independently after tumor progression to final outcome," they wrote.

The researchers reported that they had no conflicts of interest.

CHICAGO — Single nucleotide polymorphisms in DNA repair genes may help predict not only metastatic capacity but also survival in patients with primary cutaneous melanoma, according to a 400-patient study presented as a poster at the annual meeting of the American Society of Clinical Oncology.

Dr. Dirk Schadendorf of the skin cancer unit of the German Cancer Research Center in Heidelberg, Germany, and his coauthors genotyped 13 single-nucleotide polymorphisms (SNPs) from eight different DNA repair genes in 400 cutaneous melanoma patients. Average patient follow-up was 3.7 years, with 46% of patients having metastasis during that period.

The researchers found that melanoma patients with the AA genotype for the R399Q XRCC1 polymorphism showed better overall survival (hazard ratio, 0.32; P = .03) and metastasis-free survival (HR, 0.40; P = .007) compared with patients who were heterozygous and homozygous (GG). However, survival following metastasis was comparable between the groups.

The study also found that patients with AG and GG genotypes for the −1842 XRCC3 polymorphism (1843bp 5′ of the start codon in the promoter region) showed decreased survival following metastasis, although these differences in mortality after metastasis were significant only for the AG genotype (HR, 1.99; P = .003 [for AG]; HR, 1.53; P = .5 [for GG]) as was mortality overall (HR, 1.68; P = .02 for AG), compared with patients who were homozygous (AA). Metastasis-free survival did not differ between the groups.

No association was found for the other nine SNPs.

"Genetic stability, at least during a specific phase of tumor development, appears to be necessary for a malignant melanoma cell to give rise to metastasis. Accordingly, impaired repair functionality could account for reduced metastatic capacity, better metastasis-free survival, and overall survival as observed in patients homozygous for the variant allele for the R399Q XRCC1 and the K751Q ERCC2 polymorphisms in our study," the researchers wrote.

"Our data support the concept that overall survival is a sum of factors influencing time from diagnosis of the primary [cancer] to first relapse and factors contributing independently after tumor progression to final outcome," they wrote.

The researchers reported that they had no conflicts of interest.

CHICAGO — Single nucleotide polymorphisms in DNA repair genes may help predict not only metastatic capacity but also survival in patients with primary cutaneous melanoma, according to a 400-patient study presented as a poster at the annual meeting of the American Society of Clinical Oncology.

Dr. Dirk Schadendorf of the skin cancer unit of the German Cancer Research Center in Heidelberg, Germany, and his coauthors genotyped 13 single-nucleotide polymorphisms (SNPs) from eight different DNA repair genes in 400 cutaneous melanoma patients. Average patient follow-up was 3.7 years, with 46% of patients having metastasis during that period.

The researchers found that melanoma patients with the AA genotype for the R399Q XRCC1 polymorphism showed better overall survival (hazard ratio, 0.32; P = .03) and metastasis-free survival (HR, 0.40; P = .007) compared with patients who were heterozygous and homozygous (GG). However, survival following metastasis was comparable between the groups.

The study also found that patients with AG and GG genotypes for the −1842 XRCC3 polymorphism (1843bp 5′ of the start codon in the promoter region) showed decreased survival following metastasis, although these differences in mortality after metastasis were significant only for the AG genotype (HR, 1.99; P = .003 [for AG]; HR, 1.53; P = .5 [for GG]) as was mortality overall (HR, 1.68; P = .02 for AG), compared with patients who were homozygous (AA). Metastasis-free survival did not differ between the groups.

No association was found for the other nine SNPs.

"Genetic stability, at least during a specific phase of tumor development, appears to be necessary for a malignant melanoma cell to give rise to metastasis. Accordingly, impaired repair functionality could account for reduced metastatic capacity, better metastasis-free survival, and overall survival as observed in patients homozygous for the variant allele for the R399Q XRCC1 and the K751Q ERCC2 polymorphisms in our study," the researchers wrote.

"Our data support the concept that overall survival is a sum of factors influencing time from diagnosis of the primary [cancer] to first relapse and factors contributing independently after tumor progression to final outcome," they wrote.

The researchers reported that they had no conflicts of interest.