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The encouraging results of a small study of women with ductal carcinoma in situ comparing oral tamoxifen to a gel formulation of a tamoxifen metabolite support further testing of local transdermal therapy, investigators report.
The data "support the notion that local transdermal drug delivery to the breast will achieve sufficient drug concentrations to be effective, with low systemic exposure," wrote the authors, led by Dr. Oukseub Lee of the Robert H. Lurie Cancer Center of Northwestern University, Chicago. The study was published on July 15 in Clinical Cancer Research (Clin. Cancer Res. 2014;20:3672-82).
The randomized, double-blind, phase II study compared transdermal application of a gel containing 4-hydroxytamoxifen (4-OHT), an antiestrogenic metabolite of tamoxifen (4 mg/day), to oral tamoxifen (20 mg/day) in pre- and postmenopausal women with estrogen receptor–positive ductal carcinoma in situ (DCIS). Women were treated for a median of 6 weeks, between the time of the diagnostic core needle biopsy and surgical excision.
Among the 26 women who completed the study (14 on oral treatment and 12 on topical treatment), the drop in a marker for cancer cell growth (Ki-67) in the breast tissue was similar in both groups – based on comparisons of tissue from the core biopsy and the surgical excision. The mean concentration of 4-OHT in the breasts was also similar in the two groups, but mean plasma 4-OHT levels were about fivefold higher among those on oral tamoxifen (1.1 ng/mL vs. 0.2 ng/mL). Increases in coagulation-related proteins were detected among those on oral tamoxifen, but not in the women on topical treatment. The rate of hot flashes was not different in the two groups.
"Delivering the drug through a gel, if proven effective in larger trials, could potentially replace oral tamoxifen for breast cancer prevention and DCIS and encourage many more women to take it," another author, surgical oncologist Dr. Seema Khan, said in a press release on the results issued by Northwestern on July 15. "The gel minimized exposure to the rest of the body and concentrated the drug in the breast where it is needed, ... which should avoid potential blood clots as well as an elevated risk for uterine cancer," added Dr. Khan, professor of surgery and coleader of the breast cancer program at the Lurie cancer center.
The authors, which included others from Northwestern University; Washington University, St. Louis; and the National Cancer Institute, Bethesda, Md.; had no disclosures. The study was funded by the National Institutes of Health and BHR Pharma.
The encouraging results of a small study of women with ductal carcinoma in situ comparing oral tamoxifen to a gel formulation of a tamoxifen metabolite support further testing of local transdermal therapy, investigators report.
The data "support the notion that local transdermal drug delivery to the breast will achieve sufficient drug concentrations to be effective, with low systemic exposure," wrote the authors, led by Dr. Oukseub Lee of the Robert H. Lurie Cancer Center of Northwestern University, Chicago. The study was published on July 15 in Clinical Cancer Research (Clin. Cancer Res. 2014;20:3672-82).
The randomized, double-blind, phase II study compared transdermal application of a gel containing 4-hydroxytamoxifen (4-OHT), an antiestrogenic metabolite of tamoxifen (4 mg/day), to oral tamoxifen (20 mg/day) in pre- and postmenopausal women with estrogen receptor–positive ductal carcinoma in situ (DCIS). Women were treated for a median of 6 weeks, between the time of the diagnostic core needle biopsy and surgical excision.
Among the 26 women who completed the study (14 on oral treatment and 12 on topical treatment), the drop in a marker for cancer cell growth (Ki-67) in the breast tissue was similar in both groups – based on comparisons of tissue from the core biopsy and the surgical excision. The mean concentration of 4-OHT in the breasts was also similar in the two groups, but mean plasma 4-OHT levels were about fivefold higher among those on oral tamoxifen (1.1 ng/mL vs. 0.2 ng/mL). Increases in coagulation-related proteins were detected among those on oral tamoxifen, but not in the women on topical treatment. The rate of hot flashes was not different in the two groups.
"Delivering the drug through a gel, if proven effective in larger trials, could potentially replace oral tamoxifen for breast cancer prevention and DCIS and encourage many more women to take it," another author, surgical oncologist Dr. Seema Khan, said in a press release on the results issued by Northwestern on July 15. "The gel minimized exposure to the rest of the body and concentrated the drug in the breast where it is needed, ... which should avoid potential blood clots as well as an elevated risk for uterine cancer," added Dr. Khan, professor of surgery and coleader of the breast cancer program at the Lurie cancer center.
The authors, which included others from Northwestern University; Washington University, St. Louis; and the National Cancer Institute, Bethesda, Md.; had no disclosures. The study was funded by the National Institutes of Health and BHR Pharma.
The encouraging results of a small study of women with ductal carcinoma in situ comparing oral tamoxifen to a gel formulation of a tamoxifen metabolite support further testing of local transdermal therapy, investigators report.
The data "support the notion that local transdermal drug delivery to the breast will achieve sufficient drug concentrations to be effective, with low systemic exposure," wrote the authors, led by Dr. Oukseub Lee of the Robert H. Lurie Cancer Center of Northwestern University, Chicago. The study was published on July 15 in Clinical Cancer Research (Clin. Cancer Res. 2014;20:3672-82).
The randomized, double-blind, phase II study compared transdermal application of a gel containing 4-hydroxytamoxifen (4-OHT), an antiestrogenic metabolite of tamoxifen (4 mg/day), to oral tamoxifen (20 mg/day) in pre- and postmenopausal women with estrogen receptor–positive ductal carcinoma in situ (DCIS). Women were treated for a median of 6 weeks, between the time of the diagnostic core needle biopsy and surgical excision.
Among the 26 women who completed the study (14 on oral treatment and 12 on topical treatment), the drop in a marker for cancer cell growth (Ki-67) in the breast tissue was similar in both groups – based on comparisons of tissue from the core biopsy and the surgical excision. The mean concentration of 4-OHT in the breasts was also similar in the two groups, but mean plasma 4-OHT levels were about fivefold higher among those on oral tamoxifen (1.1 ng/mL vs. 0.2 ng/mL). Increases in coagulation-related proteins were detected among those on oral tamoxifen, but not in the women on topical treatment. The rate of hot flashes was not different in the two groups.
"Delivering the drug through a gel, if proven effective in larger trials, could potentially replace oral tamoxifen for breast cancer prevention and DCIS and encourage many more women to take it," another author, surgical oncologist Dr. Seema Khan, said in a press release on the results issued by Northwestern on July 15. "The gel minimized exposure to the rest of the body and concentrated the drug in the breast where it is needed, ... which should avoid potential blood clots as well as an elevated risk for uterine cancer," added Dr. Khan, professor of surgery and coleader of the breast cancer program at the Lurie cancer center.
The authors, which included others from Northwestern University; Washington University, St. Louis; and the National Cancer Institute, Bethesda, Md.; had no disclosures. The study was funded by the National Institutes of Health and BHR Pharma.
FROM CLINICAL CANCER RESEARCH
Key clinical point: The use of a topical formulation of tamoxifen applied directly to the breast could achieve the same benefits as oral tamoxifen, but with fewer systemic effects, in the treatment of ductal carcinoma in situ (DCIS) or prevention of breast cancer.
Major finding: Concentrations of the tamoxifen metabolite 4-OHT and evidence of anticancer effects in breast tissue were comparable after 6-10 weeks of treatment in women treated with a gel formulation of 4-OHT and those treated with oral tamoxifen, but coagulation markers and 4-OHT levels in the plasma were higher among those on oral medication.
Data source: A phase II, double-blind, placebo-controlled study compared antiproliferative effects, breast tissue and plasma levels of 4-OHT, and coagulation parameters in 26 women with DCIS, randomized to daily treatment with 4-OHT gel applied to both breasts or oral tamoxifen, after 6-10 weeks of treatment, ending the day before surgical excision.
Disclosures: The authors had no disclosures. The study was funded by the National Institutes of Health and BHR Pharma.