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Identifying and Managing Toxicities From Pembrolizumab CombinationsWhen pembrolizumab is combined with immunotherapies, the incidence of grade 3 to 5 toxicities increases, especially with anti–CTLA-4 combinations.
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Making the Most of the ASCO Annual MeetingWe present some tips and advice from the editorial board of ONCOLOGY on how to make the most at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, including places to go in Chicago, nice spots at McCormick Place, and some recommended presentations and sessions.
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Pediatric Neuro-Oncology: Time to Go MolecularOne recurring theme from genomic studies of pediatric CNS tumors (and almost all cancers, for that matter) is that tumors that historically appeared to be a single entity based on examination under the microscope and routine immunohistochemical staining actually harbor molecularly distinct subgroups when analyzed by genomic sequencing techniques.
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Multidisciplinary Management of Breast Cancer Brain MetastasesThis review summarizes the most up-to-date approach to the multidisciplinary management of patients with breast cancer brain metastases.
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Is There a Role for LHRH Antagonists in Prostate Cancer?The recent US Food and Drug Administration (FDA) approval of degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, has renewed interest in this class of drugs as a prostate cancer therapy. Approval was based on a prospective phase III trial of 610 patients randomized to one of two dosing schedules of degarelix, or standard-of-care monthly leuprolide acetate monotherapy, with initial antiandrogen therapy allowed at the treating physician’s discretion for prevention of clinical flare.[1]
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Hematopoietic Stem Cell Transplantation in the ElderlyHematopoietic stem cell (HSC) transplantation may improve outcomes of patients with hematologic malignancies not curable with conventional therapies. In some clinical settings, transplantation represents the only curative option. The feasibility and efficacy of this approach in older patients are undefined, since this population has been excluded from nearly all clinical trials. Advances in supportive care, HSC harvesting, and safer conditioning regimens have made this therapy available to patients well into their 6th and 7th decades of life. Recent evidence suggests that elderly patients with good performance status and no comorbidities could, in fact, not only survive the transplant with reasonable risk, but also benefit in the same measure as younger patients.
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Health-Care Disparities, Civil Rights, and Human RightsWith regard to cancer management, minority populations do not fare as well as the majority in the US health-care system. There is clear evidence of an increased incidence of cancer in minority populations, in many cases accompanied by reduced survival. Several factors appear to contribute to these differences, and the biomedical community has begun to focus on definining the scope of the problem and possible solutions. This review will address specific areas of disparity in cancer care, including prevention, diagnosis, treatment, and outcomes, and will consider steps toward resolving these issues.
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Low-Dose Spiral CT Screening and Evaluation of the Solitary Pulmonary NoduleThe number of lesions detected with low-dose CT, only some of which are early cancers, is so great that algorithms are being developed for more efficient evaluation and management of solitary pulmonary nodules. This article will discuss current tools, approaches, and concerns regarding patient care in this setting.
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The Natural History of Hormone Receptor–Positive Breast CancerIn this article, we describe the long natural history of HR+ breast cancer and review current research and clinical strategies to address this clinical challenge.
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A Fitting Prescription for All:Whole Soyfoods as Part of aVaried Plant-Based DietUntil better evidence is available for the effects of soy on women from non–soy-consuming countries, it seems reasonable to limit consumption to soyfoods, and to avoid high-dose supplements of processed soy components.
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Resolving Confusion: The New Realities of Mantle Cell LymphomaIn their Areas of Confusion article, “Management of Relapsed Mantle Cell Lymphoma: Still a Treatment Challenge,” Ruan et al attempt to make the case that the relative merits of different upfront approaches for mantle cell lymphoma (MCL) are difficult to appreciate due to the differences in eligible patient populations and limited randomized data.
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Therapeutic Activity of Humanized Anti-CD20 Monoclonal Antibody and Polymorphism in IgG FcReceptor FcgRIIIa GeneRituximab (Rituxan) is a chimeric IgG1 anti-CD20 monoclonal antibody increasingly used in the treatment of non-Hodgkin’s lymphoma (NHL). Previous in vitro studies have suggested the role of antibody-dependent cellular cytotoxicity (ADCC) and FcgR-positive effector cells (natural killer and macrophage) in the antitumor effects of anti-CD20 antibodies, but the actual mechanism of rituximab action in vivo remains largely unknown. The FCGR3A gene coding for the FcgRIIIa receptor displays a functional dimorphism with either a phenylalanine (FCGR3A-158F) or a valine (FCGR3A-158V) at amino acid 158, with a higher affinity of human IgG1 and increased ADCC for the latter. The aim of this study was thus to determine the influence of this FCGR3A polymorphism on clinical and molecular responses to rituximab.
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Radiotherapy Versis Chemotherapy as ConsolidativeTreatment for Stage IIIB-IV Hodgkin’s Disease in First Complete Remission or Good Partial Response: A Study of 559 Patients (H89 Protocol)The role of radiotherapy in combination with chemotherapy in advanced-stage Hodgkin’s disease remains controversial.
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Therapeutic Activity of Humanized Anti-CD20 Monoclonal Antibody and Polymorphism in IgG FcReceptor FcgRIIIa GeneRituximab (Rituxan) is a chimeric IgG1 anti-CD20 monoclonal antibody increasingly used in the treatment of non-Hodgkin’s lymphoma (NHL). Previous in vitro studies have suggested the role of antibody-dependent cellular cytotoxicity (ADCC) and FcgR-positive effector cells (natural killer and macrophage) in the antitumor effects of anti-CD20 antibodies, but the actual mechanism of rituximab action in vivo remains largely unknown. The FCGR3A gene coding for the FcgRIIIa receptor displays a functional dimorphism with either a phenylalanine (FCGR3A-158F) or a valine (FCGR3A-158V) at amino acid 158, with a higher affinity of human IgG1 and increased ADCC for the latter. The aim of this study was thus to determine the influence of this FCGR3A polymorphism on clinical and molecular responses to rituximab.
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Thalidomide-Induced Cessation of Weight Loss and Improved Sleep in Advanced Cancer Patients With CachexiaThe cachexia of malignancy is considered mediated through excess production of tumor necrosis factor–alpha and other cytokines. Thalidomide (Thalomid), a sedative/hypnotic, has been shown to inhibit tumor necrosis factor–alpha production.
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Nurse Practitioners Communicating Bad News to Cancer PatientsIn this video from the 2015 ONS meeting, Dr. Gwyn talks about nurse practitioners delivering bad news to patients by utilizing the SPIKES protocol.
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Efficiency of In Vivo Purging With Rituximab Followed by High-Dose Therapy With Autologous Peripheral Blood Stem Cell Transplantation in B-Cell Non-Hodgkin’s Lymphomas: A Single-Institution StudyHigh-dose therapy (HDT) with peripheral blood stem cell transplantation is a treatment option for patients with advanced follicular, marginal, and mantle cell lymphoma. In this setting, frequent contamination of peripheral blood stem cell harvests by
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Relapsed Follicular Lymphoma: Response to a Fludarabine/Mitoxantrone Regimen and the Monoclonal Anti-CD20 Antibody RituximabOur objective was to determine the efficacy of a fludarabine (Fludara)/mitoxantrone (Novantrone) regimen combined with the monoclonal anti-CD20 antibody rituximab (Rituxan) to induce clinical and molecular remissions in patients with relapsed
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Commentary (Hoskin): Evaluation and Definitive Management of Medically Inoperable Early Stage Non-Small-Cell Lung CancerLung cancer is estimated to be the second most commonly diagnosed cancer in both men and women in 2006, and the leading cause of cancer mortality. Non-small-cell lung cancer represents the majority of such cases. Most of these patients have locally advanced disease at presentation and are not eligible for curative resection. For the minority of patients who are technically resectable at presentation, lobectomy or pneumonectomy and pathologic mediastinal nodal staging offer the best overall survival. The high rate of comorbid medical illness and poor baseline pulmonary function in this population, however, make many such early-stage patients medically inoperable. For these patients, conventional single-modality radiotherapy has been the primary definitive treatment option, as discussed in part 1 of this article, which appeared in last month's issue. Numerous retrospective reports demonstrate long-term disease-free and overall survival data that are modestly superior to that expected after observation, but both local and distant failure continue to be significant risks. Investigation of radiotherapy dose escalation is ongoing, in an effort to improve local control while maintaining minimal toxicity. Additionally, emerging evidence suggests that new modalities, such as stereotactic radiosurgery and radiofrequency ablation, may also be potentially curative treatment alternatives. These modalities are addressed in part 2.
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Systematic Review of Controlled Trials on Erythropoietin to Support Evidence-Based GuidelinesTo support evidence-based clinical guidelines on erythropoietin use for anemia in oncology, we conducted systematic reviews of controlled trials on four patient groups. These were patients with treatment-related anemia; patients with disease-related anemia; patients transplanted with allogeneic hematopoietic stem cells; and those transplanted with autologous hematopoietic stem cells.
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Bone Biology and the Role of the RANK Ligand PathwayBone renewal is essential for bone strength. During childhood and early adulthood, bone formation prevails over bone resorption, as bones increase in size and strength. Peak bone mass is achieved during the third decade in life, with a higher peak bone mass being protective against osteoporosis later in life.[1] Bone loss is most prominent in women at menopause due to the effects of a natural decline in estrogen levels. However, bone mass begins to decrease with age, and bone loss is most prominent in women at menopause due to the effects of a natural decline in estrogen levels.[2]
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HER2-Positive Breast Cancer: Remaining ChallengesIn their article, "Trastuzumab and Beyond: New Possibilities for the Treatment of HER2-Positive Breast Cancer," Drs. Morris and Carey provide an excellent summary of therapeutic progress in this disease, and also turn their attention to the challenge now facing us--that of understanding the heterogeneity of HER2-positive breast cancer and mechanisms of resistance to trastuzumab (Herceptin)-based therapy.
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Radiotherapy Versis Chemotherapy as ConsolidativeTreatment for Stage IIIB-IV Hodgkin’s Disease in First Complete Remission or Good Partial Response: A Study of 559 Patients (H89 Protocol)The role of radiotherapy in combination with chemotherapy in advanced-stage Hodgkin’s disease remains controversial.
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Genetic Counseling in Hereditary Nonpolyposis Colorectal CancerRecent identification of gene mutations responsible for hereditary nonpolyposis colorectal cancer (HNPCC) has made possible the presymptomatic diagnosis of at-risk family members. If DNA testing shows that a family member is a gene carrier, that individual's lifetime cancer risk is approximately 90%. If the test is negative, the family member's cancer risk drops to that of the general population.
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Consolidation TherapyWe previously reported the efficacy of concurrent cisplatin (Platinol)/etoposide (PE) and radiotherapy in stage IIIB non–small-cell lung cancer in which biopsy confirmation of T4 (noneffusion) or N3 status was required (S9019). In view of the activity of docetaxel (Taxotere) as second-line therapy and potential molecular mechanisms of action favoring taxane sequencing, we designed the present study to maintain a core of concurrent PE/radiotherapy, but to substitute docetaxel consolidation for the two additional cycles of PE.
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Rituximab May Overcome bcl-2–Associated Chemotherapy Resistance in Untreated Diffuse Large B-Cell LymphomasThe antiapoptotic protein bcl-2 is associated with chemotherapy failure in untreated large B-cell lymphomas, and with the recently described poor-prognosis large B-cell lymphoma subtype displaying an activated B-cell genotype (Nature 403:503, 2000).
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mUC: Duration of Maintenance Avelumab and Treatment at ProgressionFocused discussion on the duration of maintenance avelumab for metastatic urothelial carcinoma and considerations for switching therapy.
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Neoadjuvant Therapy With Cisplatin/Fluorouracil vs Cisplatin/UFT in Locally Advanced Squamous Cell Head and Neck CancerThis study compared the activity and toxicity of fluorouracil (5-FU)/cisplatin with the combination tegafur and uracil (UFT)/cisplatin in the neoadjuvant treatment of locally advanced-stage III or IV (M0)-head and neck
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HER2 Overexpression and Paclitaxel Sensitivity in Breast Cancer: Therapeutic ImplicationsOverexpression by the HER2 gene plays a significant role in breast cancer pathogenesis, and the phenomenon is commonly regarded as a predictor of a poor prognosis. HER2 overexpression has been linked to sensitivity and/or resistance to hormone therapy and chemotherapeutic regimens, including CMF (cyclophosphamide, methotrexate, and fluoro-uracil) and anthracyclines. Studies of patients with advanced disease demonstrate that, despite the association of HER2 overexpression with poor prognosis, the odds of HER2-positive patients responding clinically to taxanes were greater than three times those of HER2-negative patients. Further studies in preclinical models used combination therapy for breast cancer cells that overexpress HER2, and the use of agents that interfere with HER2 function plus paclitaxel (Taxol) resulted in significant antitumor effects. [ONCOLOGY 11(Suppl):43-48, 1997]
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In Vivo Purging With Rituximab Prior to Stem Cell Collection Is Associated With Persistent Molecular Evidence of t(14;18) That Often Disappears Post-Transplant in Patients With Follicular LymphomaWe previously reported that “in vivo purging” with rituximab (Rituxan) during stem-cell collection is safe and does not adversely affect engraftment. We now report on our transplant experience with rituximab. From June 1998 to December
