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Split-dose R-CHOP: a new approach to administer cytotoxic chemo-immunotherapy to elderly patients with DLBCL
Background Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. It is challenging to deliver standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in the very elderly or elderly with comorbidities because of age-related changes in metabolism and performance.
Objectives To describe outcomes of a unique approach to the delivery of standard R-CHOP chemotherapy in split-doses for the treatment of elderly DLBCL patients.
Methods We performed a single center, retrospective analysis of all patients with DLBCL treated with split-dose R-CHOP during January 2007-April 2015. The patients received R-CHOP at a 50% dose reduction on days 1 and 15 of each 28-day cycle (split dose), with full dose rituximab on day 1 for up to 6 cycles. The total amount of chemotherapy delivered during each 28-day cycle of split-dose R-CHOP was equivalent to the cumulative dose in each 21-day cycle of standard R-CHOP.
Results We identified 22 patients who had been treated with split-dose R-CHOP (median age, 81 years). 10 patients had a Charlson Comorbidity Index score of 2 or more, and 13 were aged 80 or older. 12 patients completed their prescribed treatments, and 10 required further de-escalation or early termination owing to toxicity. All of the patients who completed therapy were in a complete remission at the end of treatment. The median overall survival for the entire cohort was 47 months, and median progression-free survival was 43 months.
Limitations Retrospective, single institution study, small cohort Conclusions Split-dose R-CHOP allowed administration of curative-intent therapy in an elderly population with encouraging outcomes.
Conclusions Split-dose R-CHOP allowed administration of curative-intent therapy in an elderly population with encouraging outcomes.
Funding/sponsorship Cancer Center Research Training Program, NCI 5-T32 CA09615-25 (fellowship funding for Dr Shah).
Click on the PDF icon at the top of this introduction to read the full article.
Background Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. It is challenging to deliver standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in the very elderly or elderly with comorbidities because of age-related changes in metabolism and performance.
Objectives To describe outcomes of a unique approach to the delivery of standard R-CHOP chemotherapy in split-doses for the treatment of elderly DLBCL patients.
Methods We performed a single center, retrospective analysis of all patients with DLBCL treated with split-dose R-CHOP during January 2007-April 2015. The patients received R-CHOP at a 50% dose reduction on days 1 and 15 of each 28-day cycle (split dose), with full dose rituximab on day 1 for up to 6 cycles. The total amount of chemotherapy delivered during each 28-day cycle of split-dose R-CHOP was equivalent to the cumulative dose in each 21-day cycle of standard R-CHOP.
Results We identified 22 patients who had been treated with split-dose R-CHOP (median age, 81 years). 10 patients had a Charlson Comorbidity Index score of 2 or more, and 13 were aged 80 or older. 12 patients completed their prescribed treatments, and 10 required further de-escalation or early termination owing to toxicity. All of the patients who completed therapy were in a complete remission at the end of treatment. The median overall survival for the entire cohort was 47 months, and median progression-free survival was 43 months.
Limitations Retrospective, single institution study, small cohort Conclusions Split-dose R-CHOP allowed administration of curative-intent therapy in an elderly population with encouraging outcomes.
Conclusions Split-dose R-CHOP allowed administration of curative-intent therapy in an elderly population with encouraging outcomes.
Funding/sponsorship Cancer Center Research Training Program, NCI 5-T32 CA09615-25 (fellowship funding for Dr Shah).
Click on the PDF icon at the top of this introduction to read the full article.
Background Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. It is challenging to deliver standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in the very elderly or elderly with comorbidities because of age-related changes in metabolism and performance.
Objectives To describe outcomes of a unique approach to the delivery of standard R-CHOP chemotherapy in split-doses for the treatment of elderly DLBCL patients.
Methods We performed a single center, retrospective analysis of all patients with DLBCL treated with split-dose R-CHOP during January 2007-April 2015. The patients received R-CHOP at a 50% dose reduction on days 1 and 15 of each 28-day cycle (split dose), with full dose rituximab on day 1 for up to 6 cycles. The total amount of chemotherapy delivered during each 28-day cycle of split-dose R-CHOP was equivalent to the cumulative dose in each 21-day cycle of standard R-CHOP.
Results We identified 22 patients who had been treated with split-dose R-CHOP (median age, 81 years). 10 patients had a Charlson Comorbidity Index score of 2 or more, and 13 were aged 80 or older. 12 patients completed their prescribed treatments, and 10 required further de-escalation or early termination owing to toxicity. All of the patients who completed therapy were in a complete remission at the end of treatment. The median overall survival for the entire cohort was 47 months, and median progression-free survival was 43 months.
Limitations Retrospective, single institution study, small cohort Conclusions Split-dose R-CHOP allowed administration of curative-intent therapy in an elderly population with encouraging outcomes.
Conclusions Split-dose R-CHOP allowed administration of curative-intent therapy in an elderly population with encouraging outcomes.
Funding/sponsorship Cancer Center Research Training Program, NCI 5-T32 CA09615-25 (fellowship funding for Dr Shah).
Click on the PDF icon at the top of this introduction to read the full article.
Lessons learned from using CDK 4/6 inhibitors to treat metastatic breast cancer
45 new cancer drugs – a significant jump from the average 26 approvals annually from 2006 to 2014. This major shift in the number of approvals is due to many factors, including the intensified efforts by scientists and clinicians to develop new drugs, especially novel immunotherapies, and changes in the FDA’s drug approval process under the leadership of Dr Richard Pazdur.
Click on the PDF icon at the top of this introduction to read the full article.
45 new cancer drugs – a significant jump from the average 26 approvals annually from 2006 to 2014. This major shift in the number of approvals is due to many factors, including the intensified efforts by scientists and clinicians to develop new drugs, especially novel immunotherapies, and changes in the FDA’s drug approval process under the leadership of Dr Richard Pazdur.
Click on the PDF icon at the top of this introduction to read the full article.
45 new cancer drugs – a significant jump from the average 26 approvals annually from 2006 to 2014. This major shift in the number of approvals is due to many factors, including the intensified efforts by scientists and clinicians to develop new drugs, especially novel immunotherapies, and changes in the FDA’s drug approval process under the leadership of Dr Richard Pazdur.
Click on the PDF icon at the top of this introduction to read the full article.
Slow and steady progress in managing gynecologic cancer
Slow but steady progress has been made in the management of the major types of gynecologic malignancy, with particularly significant advancements in the treatment of the biggest killer, ovarian cancer. Here we describe how that progress has shaped the current treatment landscape and is forging a path forward.
A therapeutic challenge
More than 90,000 new cases of gynecologic malignancy are diagnosed in the United States each year, and about a third of patients will ultimately succumb to their disease.1 Five major tumor types make up this large and varied group of cancers: cervical, ovarian, endometrial, vaginal, and vulvar, each with unique biology, etiology, and pathology.2
Most cervical cancers are squamous cell carcinomas and are caused by infection with human papillomaviruses (HPVs), a group of more than 200 related viruses. Development of effective screening methods and prophylactic vaccination have driven a substantial reduction in the incidence of cervical cancer in developed countries, though it remains a major cause of mortality in developing countries.
Click on the PDF icon at the top of this introduction to read the full article.
Slow but steady progress has been made in the management of the major types of gynecologic malignancy, with particularly significant advancements in the treatment of the biggest killer, ovarian cancer. Here we describe how that progress has shaped the current treatment landscape and is forging a path forward.
A therapeutic challenge
More than 90,000 new cases of gynecologic malignancy are diagnosed in the United States each year, and about a third of patients will ultimately succumb to their disease.1 Five major tumor types make up this large and varied group of cancers: cervical, ovarian, endometrial, vaginal, and vulvar, each with unique biology, etiology, and pathology.2
Most cervical cancers are squamous cell carcinomas and are caused by infection with human papillomaviruses (HPVs), a group of more than 200 related viruses. Development of effective screening methods and prophylactic vaccination have driven a substantial reduction in the incidence of cervical cancer in developed countries, though it remains a major cause of mortality in developing countries.
Click on the PDF icon at the top of this introduction to read the full article.
Slow but steady progress has been made in the management of the major types of gynecologic malignancy, with particularly significant advancements in the treatment of the biggest killer, ovarian cancer. Here we describe how that progress has shaped the current treatment landscape and is forging a path forward.
A therapeutic challenge
More than 90,000 new cases of gynecologic malignancy are diagnosed in the United States each year, and about a third of patients will ultimately succumb to their disease.1 Five major tumor types make up this large and varied group of cancers: cervical, ovarian, endometrial, vaginal, and vulvar, each with unique biology, etiology, and pathology.2
Most cervical cancers are squamous cell carcinomas and are caused by infection with human papillomaviruses (HPVs), a group of more than 200 related viruses. Development of effective screening methods and prophylactic vaccination have driven a substantial reduction in the incidence of cervical cancer in developed countries, though it remains a major cause of mortality in developing countries.
Click on the PDF icon at the top of this introduction to read the full article.
Evolving therapeutic strategies maintain clinical momentum in melanoma
The past 5 years have witnessed a watershed moment in the management of metastatic melanoma. The successes of molecularly targeted and immune-based therapies have transformed it from an aggressively lethal malignancy into one that is readily treatable. Here, we discuss continued efforts to find new therapies and broaden the clinical impact of existing options to maintain the unprecedented momentum of improving patient outcomes.
Click on the PDF icon at the top of this introduction to read the full article.
The past 5 years have witnessed a watershed moment in the management of metastatic melanoma. The successes of molecularly targeted and immune-based therapies have transformed it from an aggressively lethal malignancy into one that is readily treatable. Here, we discuss continued efforts to find new therapies and broaden the clinical impact of existing options to maintain the unprecedented momentum of improving patient outcomes.
Click on the PDF icon at the top of this introduction to read the full article.
The past 5 years have witnessed a watershed moment in the management of metastatic melanoma. The successes of molecularly targeted and immune-based therapies have transformed it from an aggressively lethal malignancy into one that is readily treatable. Here, we discuss continued efforts to find new therapies and broaden the clinical impact of existing options to maintain the unprecedented momentum of improving patient outcomes.
Click on the PDF icon at the top of this introduction to read the full article.
More success for immunotherapy with nivolumab approval for metastatic RCC
Encouraging data on immunotherapy, cardiotoxicity, and DFS
Click on the PDF icon at the top of this introduction to read the full article.
Click on the PDF icon at the top of this introduction to read the full article.
Click on the PDF icon at the top of this introduction to read the full article.
Making immunotherapy part of routine breast cancer treatment
Cancer treatment is evolving rapidly, and 2015 was no exception. It was the year of immunotherapy. Following the approval by the US Food and Drug Administration in 2014 of pembrolizumab for melanoma, 2015 saw approvals of nivolumab for melanoma, lung cancer, and kidney cancer; pembrolizumab for lung cancer; and the combination of ipilimumab and nivolimab for melanoma. That’s an impressive list of immunotherapy approvals for a single year.
Click on the PDF icon at the top of this introduction to read the full article.
Cancer treatment is evolving rapidly, and 2015 was no exception. It was the year of immunotherapy. Following the approval by the US Food and Drug Administration in 2014 of pembrolizumab for melanoma, 2015 saw approvals of nivolumab for melanoma, lung cancer, and kidney cancer; pembrolizumab for lung cancer; and the combination of ipilimumab and nivolimab for melanoma. That’s an impressive list of immunotherapy approvals for a single year.
Click on the PDF icon at the top of this introduction to read the full article.
Cancer treatment is evolving rapidly, and 2015 was no exception. It was the year of immunotherapy. Following the approval by the US Food and Drug Administration in 2014 of pembrolizumab for melanoma, 2015 saw approvals of nivolumab for melanoma, lung cancer, and kidney cancer; pembrolizumab for lung cancer; and the combination of ipilimumab and nivolimab for melanoma. That’s an impressive list of immunotherapy approvals for a single year.
Click on the PDF icon at the top of this introduction to read the full article.
Entering an era of intelligent combination therapy in cancer
The past few decades have witnessed unprecedented advances in our understanding of the molecular underpinnings of cancer. Although indiscriminately cytotoxic therapies like chemo- and radiation therapy remain standard of care for many cancer types, more precise targeted therapies and immune-boosting immunotherapies have added to our arsenal and afforded considerable survival gains. Despite those advances, we are still no closer to a cure, particularly for the most aggressive and insidious cancers that progress rapidly or go undiagnosed until advanced stages of disease. The substantial genetic diversity of tumors and universal nature of drug resistance present the most formidable and enduring challenges to effective cancer treatment.
Click on the PDF icon at the top of this introduction to read the full article.
The past few decades have witnessed unprecedented advances in our understanding of the molecular underpinnings of cancer. Although indiscriminately cytotoxic therapies like chemo- and radiation therapy remain standard of care for many cancer types, more precise targeted therapies and immune-boosting immunotherapies have added to our arsenal and afforded considerable survival gains. Despite those advances, we are still no closer to a cure, particularly for the most aggressive and insidious cancers that progress rapidly or go undiagnosed until advanced stages of disease. The substantial genetic diversity of tumors and universal nature of drug resistance present the most formidable and enduring challenges to effective cancer treatment.
Click on the PDF icon at the top of this introduction to read the full article.
The past few decades have witnessed unprecedented advances in our understanding of the molecular underpinnings of cancer. Although indiscriminately cytotoxic therapies like chemo- and radiation therapy remain standard of care for many cancer types, more precise targeted therapies and immune-boosting immunotherapies have added to our arsenal and afforded considerable survival gains. Despite those advances, we are still no closer to a cure, particularly for the most aggressive and insidious cancers that progress rapidly or go undiagnosed until advanced stages of disease. The substantial genetic diversity of tumors and universal nature of drug resistance present the most formidable and enduring challenges to effective cancer treatment.
Click on the PDF icon at the top of this introduction to read the full article.
Dinutuximab combination therapy becomes first approval for high-risk neuroblastoma
The mAb was approved in combination with the cytokines granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2), and the oral retinoid isotretinoin (RA). The approval was based on a pivotal, phase 3, multicenter, open-label, randomized trial conducted by the Children’s Oncology Group between October 2001 and January 2009 that was stopped early after the combination demonstrated superiority over standard therapy with respect to event-free survival (EFS).2
Two hundred and twenty-six patients (mostly pediatric patients, though age up to 31 years at diagnosis was allowed) with high-risk neuroblastoma were enrolled based on the following criteria: age of ≤31 years at diagnosis; completion of induction therapy, autologous stem-cell transplant (SCT), and radiation therapy, with autologous SCT performed within 9 months of initiation of induction therapy; achievement of at least partial response prior to autologous SCT; enrollment between 50-100 days after final autologous SCT; absence of progressive disease; adequate organ function; life expectancy of at least 2 months; and prior enrollment in the COG biology study (ANBL00B1). An additional 25 patients with biopsy-proven residual disease after autologous SCT were also enrolled, but were nonrandomly assigned to the immunotherapy arm and were excluded from the primary outcome analysis. Patients with systemic infections or a requirement for concomitant systemic corticosteroids or immunosuppressant usage were ineligible.
Click on the PDF icon at the top of this introduction to read the full article.
The mAb was approved in combination with the cytokines granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2), and the oral retinoid isotretinoin (RA). The approval was based on a pivotal, phase 3, multicenter, open-label, randomized trial conducted by the Children’s Oncology Group between October 2001 and January 2009 that was stopped early after the combination demonstrated superiority over standard therapy with respect to event-free survival (EFS).2
Two hundred and twenty-six patients (mostly pediatric patients, though age up to 31 years at diagnosis was allowed) with high-risk neuroblastoma were enrolled based on the following criteria: age of ≤31 years at diagnosis; completion of induction therapy, autologous stem-cell transplant (SCT), and radiation therapy, with autologous SCT performed within 9 months of initiation of induction therapy; achievement of at least partial response prior to autologous SCT; enrollment between 50-100 days after final autologous SCT; absence of progressive disease; adequate organ function; life expectancy of at least 2 months; and prior enrollment in the COG biology study (ANBL00B1). An additional 25 patients with biopsy-proven residual disease after autologous SCT were also enrolled, but were nonrandomly assigned to the immunotherapy arm and were excluded from the primary outcome analysis. Patients with systemic infections or a requirement for concomitant systemic corticosteroids or immunosuppressant usage were ineligible.
Click on the PDF icon at the top of this introduction to read the full article.
The mAb was approved in combination with the cytokines granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2), and the oral retinoid isotretinoin (RA). The approval was based on a pivotal, phase 3, multicenter, open-label, randomized trial conducted by the Children’s Oncology Group between October 2001 and January 2009 that was stopped early after the combination demonstrated superiority over standard therapy with respect to event-free survival (EFS).2
Two hundred and twenty-six patients (mostly pediatric patients, though age up to 31 years at diagnosis was allowed) with high-risk neuroblastoma were enrolled based on the following criteria: age of ≤31 years at diagnosis; completion of induction therapy, autologous stem-cell transplant (SCT), and radiation therapy, with autologous SCT performed within 9 months of initiation of induction therapy; achievement of at least partial response prior to autologous SCT; enrollment between 50-100 days after final autologous SCT; absence of progressive disease; adequate organ function; life expectancy of at least 2 months; and prior enrollment in the COG biology study (ANBL00B1). An additional 25 patients with biopsy-proven residual disease after autologous SCT were also enrolled, but were nonrandomly assigned to the immunotherapy arm and were excluded from the primary outcome analysis. Patients with systemic infections or a requirement for concomitant systemic corticosteroids or immunosuppressant usage were ineligible.
Click on the PDF icon at the top of this introduction to read the full article.
Nivolumab: first immunotherapy approved for lung cancer
Click on the PDF icon at the top of this introduction to read the full article.
Click on the PDF icon at the top of this introduction to read the full article.
Click on the PDF icon at the top of this introduction to read the full article.