The Journal of Community and Supportive Oncology

Myelofibrosis (MF), including primary MF and MF secondary to polycythemia vera or essential thrombocythemia, is a chronic, clinically heterogeneous hematologic malignancy characterized by inefficient hematopoiesis, bone marrow fibrosis, and shortened survival. Typical clinical manifestations include progressive splenomegaly, debilitating symptoms, and anemia. MF is associated with dysregulation of Janus kinase (JAK)-signal transducer and activator of transcription (JAK/STAT) pathway affecting hematopoiesis and inflammation. Ruxolitinib, an oral JAK1/JAK2 inhibitor, was approved for the treatment of patients with intermediate or high-risk MF based on the results of 2 phase 3 studies (Controlled MyeloFibrosis Study with Oral JAK Inhibitor Treatment [COMFORT]-I and COMFORT-II). In these trials, ruxolitinib treatment was associated with reductions in spleen size and symptom burden, and improvements in quality of life. The most common adverse events were dose-dependent cytopenias, which were managed by dose modifications, treatment interruptions, and red blood cell transfusions (for anemia). Ruxolitinib was effective regardless of MF type, risk status, or JAK2V617F mutation status, and across various other MF subpopulations. Two-year follow-up data from the COMFORT trials also demonstrate that ruxolitinib has durable efficacy and may be associated with a survival advantage relative to placebo and best available therapy. Preliminary data from ongoing studies support possible dosing strategies for patients with low platelet counts.

Click on the PDF icon at the top of this introduction to read the full article.

Myelofibrosis (MF), including primary MF and MF secondary to polycythemia vera or essential thrombocythemia, is a chronic, clinically heterogeneous hematologic malignancy characterized by inefficient hematopoiesis, bone marrow fibrosis, and shortened survival. Typical clinical manifestations include progressive splenomegaly, debilitating symptoms, and anemia. MF is associated with dysregulation of Janus kinase (JAK)-signal transducer and activator of transcription (JAK/STAT) pathway affecting hematopoiesis and inflammation. Ruxolitinib, an oral JAK1/JAK2 inhibitor, was approved for the treatment of patients with intermediate or high-risk MF based on the results of 2 phase 3 studies (Controlled MyeloFibrosis Study with Oral JAK Inhibitor Treatment [COMFORT]-I and COMFORT-II). In these trials, ruxolitinib treatment was associated with reductions in spleen size and symptom burden, and improvements in quality of life. The most common adverse events were dose-dependent cytopenias, which were managed by dose modifications, treatment interruptions, and red blood cell transfusions (for anemia). Ruxolitinib was effective regardless of MF type, risk status, or JAK2V617F mutation status, and across various other MF subpopulations. Two-year follow-up data from the COMFORT trials also demonstrate that ruxolitinib has durable efficacy and may be associated with a survival advantage relative to placebo and best available therapy. Preliminary data from ongoing studies support possible dosing strategies for patients with low platelet counts.

Click on the PDF icon at the top of this introduction to read the full article.

Myelofibrosis (MF), including primary MF and MF secondary to polycythemia vera or essential thrombocythemia, is a chronic, clinically heterogeneous hematologic malignancy characterized by inefficient hematopoiesis, bone marrow fibrosis, and shortened survival. Typical clinical manifestations include progressive splenomegaly, debilitating symptoms, and anemia. MF is associated with dysregulation of Janus kinase (JAK)-signal transducer and activator of transcription (JAK/STAT) pathway affecting hematopoiesis and inflammation. Ruxolitinib, an oral JAK1/JAK2 inhibitor, was approved for the treatment of patients with intermediate or high-risk MF based on the results of 2 phase 3 studies (Controlled MyeloFibrosis Study with Oral JAK Inhibitor Treatment [COMFORT]-I and COMFORT-II). In these trials, ruxolitinib treatment was associated with reductions in spleen size and symptom burden, and improvements in quality of life. The most common adverse events were dose-dependent cytopenias, which were managed by dose modifications, treatment interruptions, and red blood cell transfusions (for anemia). Ruxolitinib was effective regardless of MF type, risk status, or JAK2V617F mutation status, and across various other MF subpopulations. Two-year follow-up data from the COMFORT trials also demonstrate that ruxolitinib has durable efficacy and may be associated with a survival advantage relative to placebo and best available therapy. Preliminary data from ongoing studies support possible dosing strategies for patients with low platelet counts.

Click on the PDF icon at the top of this introduction to read the full article.

Background and objective A cumulative review of hepatobiliary abnormalities in the lapatinib clinical program resulted in inclusion of detailed instructions for liver function test (LFT) monitoring in the US prescribing information (label). We sought to determine whether or not physicians adhere to these recommended guidelines.

Methods A retrospective observational cohort study comprising 396 women with HER2  metastatic breast cancer who initiated lapatinib between March 1, 2007 and June 30, 2010. Data were captured from electronic medical records (EMR) of communitybased oncology practices. Patients were categorized by whether they initiated lapatinib before or after the label change; LFT monitoring was evaluated using a pre- versus post-label study design. We measured the proportion of patients who had LFTs within 30 days before lapatinib initiation, LFTs during each 6-week period of treatment, and lapatinib permanently withdrawn after experiencing an extreme LFT elevation.

Results Among 396 patients, 128 (32%) initiated lapatinib pre-label change, and 268 (68%) initiated post-label change. LFTs were conducted 30 days prior to lapatinib start in 82% post-label versus 63% pre-label change patients (P greater than .001). Testing during each 6-week treatment interval was higher in post-label change patients: 81% versus 68% pre-label change patients during the first 6 weeks of therapy (P equals .004), and 83% versus 62%, respectively, during weeks 18-24 (P equals .0103). Four patients experienced a severe LFT elevation: 2 pre-label patients who resumed treatment, and 2 post-label change patients with complete discontinuation.

Conclusions We demonstrated that LFT monitoring increased after the addition of detailed LFT guidance to the lapatinib label.

*Click on the link to the left for a PDF of the full article.  

Background and objective A cumulative review of hepatobiliary abnormalities in the lapatinib clinical program resulted in inclusion of detailed instructions for liver function test (LFT) monitoring in the US prescribing information (label). We sought to determine whether or not physicians adhere to these recommended guidelines.

Methods A retrospective observational cohort study comprising 396 women with HER2  metastatic breast cancer who initiated lapatinib between March 1, 2007 and June 30, 2010. Data were captured from electronic medical records (EMR) of communitybased oncology practices. Patients were categorized by whether they initiated lapatinib before or after the label change; LFT monitoring was evaluated using a pre- versus post-label study design. We measured the proportion of patients who had LFTs within 30 days before lapatinib initiation, LFTs during each 6-week period of treatment, and lapatinib permanently withdrawn after experiencing an extreme LFT elevation.

Results Among 396 patients, 128 (32%) initiated lapatinib pre-label change, and 268 (68%) initiated post-label change. LFTs were conducted 30 days prior to lapatinib start in 82% post-label versus 63% pre-label change patients (P greater than .001). Testing during each 6-week treatment interval was higher in post-label change patients: 81% versus 68% pre-label change patients during the first 6 weeks of therapy (P equals .004), and 83% versus 62%, respectively, during weeks 18-24 (P equals .0103). Four patients experienced a severe LFT elevation: 2 pre-label patients who resumed treatment, and 2 post-label change patients with complete discontinuation.

Conclusions We demonstrated that LFT monitoring increased after the addition of detailed LFT guidance to the lapatinib label.

*Click on the link to the left for a PDF of the full article.  

Background and objective A cumulative review of hepatobiliary abnormalities in the lapatinib clinical program resulted in inclusion of detailed instructions for liver function test (LFT) monitoring in the US prescribing information (label). We sought to determine whether or not physicians adhere to these recommended guidelines.

Methods A retrospective observational cohort study comprising 396 women with HER2  metastatic breast cancer who initiated lapatinib between March 1, 2007 and June 30, 2010. Data were captured from electronic medical records (EMR) of communitybased oncology practices. Patients were categorized by whether they initiated lapatinib before or after the label change; LFT monitoring was evaluated using a pre- versus post-label study design. We measured the proportion of patients who had LFTs within 30 days before lapatinib initiation, LFTs during each 6-week period of treatment, and lapatinib permanently withdrawn after experiencing an extreme LFT elevation.

Results Among 396 patients, 128 (32%) initiated lapatinib pre-label change, and 268 (68%) initiated post-label change. LFTs were conducted 30 days prior to lapatinib start in 82% post-label versus 63% pre-label change patients (P greater than .001). Testing during each 6-week treatment interval was higher in post-label change patients: 81% versus 68% pre-label change patients during the first 6 weeks of therapy (P equals .004), and 83% versus 62%, respectively, during weeks 18-24 (P equals .0103). Four patients experienced a severe LFT elevation: 2 pre-label patients who resumed treatment, and 2 post-label change patients with complete discontinuation.

Conclusions We demonstrated that LFT monitoring increased after the addition of detailed LFT guidance to the lapatinib label.

*Click on the link to the left for a PDF of the full article.  

With an exponential increase in the number of cancer survivors over the past few decades, we have an opportunity and responsibility to effectively manage cancer survivors across the continuum of cancer care. The delivery of survivorship care requires realistic deliverables with defined outcomes that focus on cost, impact on disease management and prevention, and integration within a health care delivery model. Building a framework using defined time-points and definitions can be helpful. Due to the complex nature of delivering cancer survivorship care, it is necessary to establish collaborations with specialty providers including cardiologists, reproductive specialists, endocrinology, ophthalmology, allied health professionals and cancer rehab, to name a few. Strengthening relationships with primary care providers will enhance the transition from cancer care to primary care. Essential tools to help fulfill these goals and achieve national standards include using expert recommended treatment summaries and survivorship care plans. These tools support a shared care model with the goal of high quality, coordinated healthcare for the survivorship population. With limited evidence to guide the delivery of survivorship care and national standards looming, how do we meet the demands of cancer survivorship? This article explores the “the who, what, when, where, why and how?” of cancer survivorship care.

Click on the PDF icon at the top of this introduction to read the full article.

With an exponential increase in the number of cancer survivors over the past few decades, we have an opportunity and responsibility to effectively manage cancer survivors across the continuum of cancer care. The delivery of survivorship care requires realistic deliverables with defined outcomes that focus on cost, impact on disease management and prevention, and integration within a health care delivery model. Building a framework using defined time-points and definitions can be helpful. Due to the complex nature of delivering cancer survivorship care, it is necessary to establish collaborations with specialty providers including cardiologists, reproductive specialists, endocrinology, ophthalmology, allied health professionals and cancer rehab, to name a few. Strengthening relationships with primary care providers will enhance the transition from cancer care to primary care. Essential tools to help fulfill these goals and achieve national standards include using expert recommended treatment summaries and survivorship care plans. These tools support a shared care model with the goal of high quality, coordinated healthcare for the survivorship population. With limited evidence to guide the delivery of survivorship care and national standards looming, how do we meet the demands of cancer survivorship? This article explores the “the who, what, when, where, why and how?” of cancer survivorship care.

Click on the PDF icon at the top of this introduction to read the full article.

With an exponential increase in the number of cancer survivors over the past few decades, we have an opportunity and responsibility to effectively manage cancer survivors across the continuum of cancer care. The delivery of survivorship care requires realistic deliverables with defined outcomes that focus on cost, impact on disease management and prevention, and integration within a health care delivery model. Building a framework using defined time-points and definitions can be helpful. Due to the complex nature of delivering cancer survivorship care, it is necessary to establish collaborations with specialty providers including cardiologists, reproductive specialists, endocrinology, ophthalmology, allied health professionals and cancer rehab, to name a few. Strengthening relationships with primary care providers will enhance the transition from cancer care to primary care. Essential tools to help fulfill these goals and achieve national standards include using expert recommended treatment summaries and survivorship care plans. These tools support a shared care model with the goal of high quality, coordinated healthcare for the survivorship population. With limited evidence to guide the delivery of survivorship care and national standards looming, how do we meet the demands of cancer survivorship? This article explores the “the who, what, when, where, why and how?” of cancer survivorship care.

Click on the PDF icon at the top of this introduction to read the full article.

Chimeric antigen receptor-modified T cells represent a new approach to immune therapy in the treatment of hematologic malignancies. The clinical activity of chimeric antigen receptors (CARs) has been published in acute lymphoblastic leukemia (ALL)and chronic lymphocytic leukemia (CLL).¹ The results have been remarkable, although only a very small number of patients have been treated. We are anticipating further clinical trials and further development of this technology for more wide spread treatment opportunities for patients. The CARs that have been the most successful clinically have a similar basic make-up. They are genetically modified T cells. The T cells are collected from the patients through leukapheresis, then they are genetically
modified to express an extracellular recognition domain that is connected in the intracellular signaling domains of the T cells. Various extracellular recognition domains have been engineered, but the target of CD19 has proven most successful in patients with B cell malignancies, and CD19 is widely expressed on CLL and B-cell ALL. The cells are infused back into the patient, sometimes after undergoing chemotherapy to lymphodeplete the patient (which may improve the recovery and persistence of the cells after treatment). The infusion responses have been
dramatic in some patients, with severe cytokine storm described in reports, usually several days after treatment.² This is thought to reflect the very rapid identification of the target protein and response of the T cells to the target. Those patients with acute leukemia who have responded also appear to respond rapidly, with disappearance of blasts from the peripheral blood within a month. The cells have been detectable in some patients for months after treatment.

Please click here to view the PDF.

Chimeric antigen receptor-modified T cells represent a new approach to immune therapy in the treatment of hematologic malignancies. The clinical activity of chimeric antigen receptors (CARs) has been published in acute lymphoblastic leukemia (ALL)and chronic lymphocytic leukemia (CLL).¹ The results have been remarkable, although only a very small number of patients have been treated. We are anticipating further clinical trials and further development of this technology for more wide spread treatment opportunities for patients. The CARs that have been the most successful clinically have a similar basic make-up. They are genetically modified T cells. The T cells are collected from the patients through leukapheresis, then they are genetically
modified to express an extracellular recognition domain that is connected in the intracellular signaling domains of the T cells. Various extracellular recognition domains have been engineered, but the target of CD19 has proven most successful in patients with B cell malignancies, and CD19 is widely expressed on CLL and B-cell ALL. The cells are infused back into the patient, sometimes after undergoing chemotherapy to lymphodeplete the patient (which may improve the recovery and persistence of the cells after treatment). The infusion responses have been
dramatic in some patients, with severe cytokine storm described in reports, usually several days after treatment.² This is thought to reflect the very rapid identification of the target protein and response of the T cells to the target. Those patients with acute leukemia who have responded also appear to respond rapidly, with disappearance of blasts from the peripheral blood within a month. The cells have been detectable in some patients for months after treatment.

Please click here to view the PDF.

Chimeric antigen receptor-modified T cells represent a new approach to immune therapy in the treatment of hematologic malignancies. The clinical activity of chimeric antigen receptors (CARs) has been published in acute lymphoblastic leukemia (ALL)and chronic lymphocytic leukemia (CLL).¹ The results have been remarkable, although only a very small number of patients have been treated. We are anticipating further clinical trials and further development of this technology for more wide spread treatment opportunities for patients. The CARs that have been the most successful clinically have a similar basic make-up. They are genetically modified T cells. The T cells are collected from the patients through leukapheresis, then they are genetically
modified to express an extracellular recognition domain that is connected in the intracellular signaling domains of the T cells. Various extracellular recognition domains have been engineered, but the target of CD19 has proven most successful in patients with B cell malignancies, and CD19 is widely expressed on CLL and B-cell ALL. The cells are infused back into the patient, sometimes after undergoing chemotherapy to lymphodeplete the patient (which may improve the recovery and persistence of the cells after treatment). The infusion responses have been
dramatic in some patients, with severe cytokine storm described in reports, usually several days after treatment.² This is thought to reflect the very rapid identification of the target protein and response of the T cells to the target. Those patients with acute leukemia who have responded also appear to respond rapidly, with disappearance of blasts from the peripheral blood within a month. The cells have been detectable in some patients for months after treatment.

Please click here to view the PDF.

Bone metastasis is a serious complication of advanced cancer. It is most commonly observed in patients with metastatic breast and prostate cancers, but also occurs in most other metastatic solid cancers. Without treatment, patients may experience complications including intractable bone pain, hypercalcemia, fracture, spinal cord compression and/or a requirement for surgical or radiotherapeutic intervention. In 2010, denosumab, a fully human monoclonal antibody that inhibits RANK ligand (RANKL) and subsequent osteoclast-mediated bone destruction, was approved by the Food and Drug Administration for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. This article reviews the role of denosumab in preventing SREs due to bone metastases, treating bone loss due to hormone-ablative cancer therapies, and describes denosumab’s safety profile and potential future indications under investigation.

Click on the PDF icon at the top of this introduction to read the full article.

Bone metastasis is a serious complication of advanced cancer. It is most commonly observed in patients with metastatic breast and prostate cancers, but also occurs in most other metastatic solid cancers. Without treatment, patients may experience complications including intractable bone pain, hypercalcemia, fracture, spinal cord compression and/or a requirement for surgical or radiotherapeutic intervention. In 2010, denosumab, a fully human monoclonal antibody that inhibits RANK ligand (RANKL) and subsequent osteoclast-mediated bone destruction, was approved by the Food and Drug Administration for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. This article reviews the role of denosumab in preventing SREs due to bone metastases, treating bone loss due to hormone-ablative cancer therapies, and describes denosumab’s safety profile and potential future indications under investigation.

Click on the PDF icon at the top of this introduction to read the full article.

Bone metastasis is a serious complication of advanced cancer. It is most commonly observed in patients with metastatic breast and prostate cancers, but also occurs in most other metastatic solid cancers. Without treatment, patients may experience complications including intractable bone pain, hypercalcemia, fracture, spinal cord compression and/or a requirement for surgical or radiotherapeutic intervention. In 2010, denosumab, a fully human monoclonal antibody that inhibits RANK ligand (RANKL) and subsequent osteoclast-mediated bone destruction, was approved by the Food and Drug Administration for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. This article reviews the role of denosumab in preventing SREs due to bone metastases, treating bone loss due to hormone-ablative cancer therapies, and describes denosumab’s safety profile and potential future indications under investigation.

Click on the PDF icon at the top of this introduction to read the full article.