bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bexxar®: Novel Radioimmunotherapy for the Treatment of Low-Grade and Transformed Low-Grade Non-Hodgkin's Lymphoma
Authors: Vose Julie M. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Describe advances in clinical radioimmunotherapy. Discuss ongoing translational research in radioimmunotherapy. Identify future directions for radioimmunotherapy in cancer medicine.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at http://CME.TheOncologist.com
Purpose. Immunotherapy using monoclonal antibodies to specifically target B cells has provided new hope to many patients with indolent lymphomas, particularly those with chemotherapy-refractory disease. Lymphomas are extremely sensitive to radiation, and significant progress has been made over the last decade in the development of radioimmunotherapy with anti-CD20 antibodies.
Materials and Methods. Herein we review clinical experience with tositumomab and iodine I 131 tositumomab (Bexxar®; Corixa Corporation; South San Francisco, CA; and GlaxoSmithKline; Philadelphia, PA) in patients with non-Hodgkin's lymphoma.
Results. Therapy with Bexxar has demonstrated high response rates and long durations of response compared with unconjugated anti-CD20 antibodies in patients with relapsed low-grade and transformed low-grade non-Hodgkin's lymphomas. Iodine-131 (I-131) has a long history of clinical experience, an excellent safety record, and favorable nuclear and pharmacologic properties. Importantly, the gamma emissions of iodine-131 facilitate accurate dosimetry to calculate the appropriate patient-specific therapeutic activity to deliver a predetermined total-body dose of radiation, thereby minimizing hematologic toxicity. In clinical trials of Bexxar, objective response rates ranged from 54%–71% in heavily pretreated patients. In the pivotal trial, the number of patients with a longer duration of response after treatment with Bexxar was significantly greater than the number of patients with a longer duration of response after their last qualifying chemotherapy regimen. In 76 newly diagnosed patients, the objective response rate was 97%, and 63% of patients achieved complete responses.
Conclusion. These data suggest that Bexxar will become an important new option in the treatment of indolent lymphoma.
Topotecan in the Treatment of Relapsed Small Cell Lung Cancer Patients with Poor Performance Status
Authors: Treat Joseph , Huang Chao Hui , Lane Stephen R. , Levin Jeremey 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Describe the hematologic safety profile of topotecan in patients with relapsed small cell lung cancer. Identify the risk factors for poorer performance status. Discuss the role of topotecan in the management of poor performance status patients with relapsed small cell lung cancer.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at http://CME.TheOncologist.com
Topotecan is the only single-agent therapy approved by the U.S. Food and Drug Administration for the treatment of patients with recurrent small cell lung cancer (SCLC). Poor performance status (PS) at the time of relapse can hinder the ability of a patient to tolerate second-line chemotherapy. To investigate the feasibility of topotecan in the treatment of relapsed SCLC patients with PS 2 scores, we retrospectively analyzed data from five clinical trials that included 479 patients who were treated with single-agent topotecan at a dose of 1.5 mg/m2/day on days 1–5 of a 21-day course. Of these patients, 381 had a PS 0 or 1 and 98 had a PS 2. Topotecan was well tolerated by both patient groups. Hematologic toxicities were generally manageable, and neutropenia was noncumulative. With the exception of grade 3/4 anemia, the incidences of severe hematologic toxicities were not statistically different between the two groups. The nonhematologic toxicity profiles were also similar in the two patient groups. Treatment provided similar benefits, including antitumor response rates and symptom palliation, in PS 0/1 and PS 2 patients. As expected, the median overall survival time was shorter in patients with worse PS scores; the median overall survival times were 36.3 weeks, 25.4 weeks, and 16 weeks for PS 0, PS 1, and PS 2 patients, respectively. In conclusion, treatment with topotecan is feasible and well tolerated in patients with relapsed SCLC with suboptimal PS scores.
Surgical Management of Spinal Metastases
Authors: Klimo Paul , Schmidt Meic H. 
Published: August 2004

Abstract
Metastatic spread to the spinal column is a growing problem in patients with cancer. It can cause a number of sequelae including pain, instability, and neurologic deficit. If left untreated, progressive myelopathy results in the loss of motor, sensory, and autonomic functions. Except in rare circumstances, treatment is palliative. Traditionally, conventional fractionated external beam radiotherapy has been the treatment of choice. “Surgery” for metastatic spinal disease was, and generally continues to be, equated with laminectomy by many physicians. However, there has been a remarkable evolution in surgical techniques over the last 20 years. Today, the goal of surgery is to achieve circumferential decompression of the neural elements while reconstructing and immediately stabilizing the spinal column. This has been made possible by the use of different surgical approaches and the exploitation of a burgeoning array of internal fixation devices. More recently, minimally invasive surgical techniques, such as endoscopy, kyphoplasty/vertebroplasty, and stereotactic radiosurgery, have been added to the surgeon's armamentarium. As the number of treatment options for metastatic spinal disease grows, it has become clear that effective implementation of treatment can only be achieved by a multidisciplinary approach. This will provide the surest means of maximizing the quality of the remainder of the patient's life.
Supratentorial High-Grade Astrocytoma and Diffuse Brainstem Glioma: Two Challenges for the Pediatric Oncologist
Authors: Broniscer Alberto , Gajjar Amar 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Describe the known genetic alterations associated with pediatric supratentorial high-grade astrocytomas and diffuse brainstem gliomas. Discuss the clinical and biologic prognostic factors for children with supratentorial high-grade astrocytomas and diffuse brainstem gliomas. Explain the roles played by surgery, radiation therapy, and chemotherapy in the treatment of children with supratentorial high-grade astrocytomas and diffuse brainstem gliomas.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at http://CME.TheOncologist.com
Pediatric high-grade gliomas represent a heterogeneous group of tumors that accounts for 15%–20% of all pediatric central nervous system tumors. These neoplasms predominantly involve the supratentorial hemispheres or the pons, in which case the tumors are usually called diffuse brainstem gliomas. The diagnosis of supratentorial neoplasms is dependent on their histologic appearance. The maximum possible surgical resection is always attempted since the degree of surgical resection is the main prognostic factor for these patients. Older children (&gt;3 years) with supratentorial neoplasms undergo a multimodality treatment comprised of surgical resection, radiation therapy, and chemotherapy. The addition of chemotherapy seems to improve the survival of a subset of these children, particularly those with glioblastoma multiforme. However, 2-year survival rates remain poor for children with supratentorial neoplasms, ranging from 10%–30%.
The diagnosis of a diffuse brainstem glioma is based upon typical imaging, dispensing with the need for surgery in the majority of cases. Radiation therapy is the mainstay of treatment for children with diffuse brainstem gliomas. The role of chemotherapy for these children is not clear, and it is, in general, employed in the context of an investigational study. Less than 10% of children with diffuse brainstem gliomas survive 2 years.
Because the outcome for patients with either type of tumor is poor when standard multimodality therapy is used, these children are ideal candidates for innovative treatment approaches.
Thrombotic Complications of Central Venous Catheters in Cancer Patients
Authors: Kuter David J. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Describe the mechanism of thrombosis in CVCs. Explain the symptoms, signs, and sequelae of CVC thrombosis. Discuss the evidence supporting the prophylaxis of CVC thrombosis.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at http://CME.TheOncologist.com
Central venous catheters (CVCs), such as the tunneled catheters and the totally implanted ports, play a major role in general medicine and oncology. Aside from the complications (pneumothorax, hemorrhage) associated with their initial insertion, all of these CVCs are associated with the long-term risks of infection and thrombosis. Despite routine flushing with heparin or saline, 41% of CVCs result in thrombosis of the blood vessel, and this markedly increases the risk of infection. Only one-third of these clots are symptomatic.
Within days of insertion, almost all CVCs are coated with a fibrin sheath, and within 30 days, most CVC-related thrombi arise. Aside from reducing the function of the catheter, these CVC-related thrombi can cause postphlebitic syndrome in 15%–30% of cases and pulmonary embolism in 11% (only half of which are symptomatic).
Risk factors for CVC thrombosis include the type of malignancy, type of chemotherapy, type of CVC, and locations of insertion site and catheter tip, but not inherited thrombophilic risk factors. Efforts to reduce CVC thrombosis with systemic prophylactic anticoagulation with low-molecular-weight heparin have failed. Low-dose warfarin prophylaxis remains controversial; all studies are flawed, with older studies, but not newer ones, showing benefit.
Currently, less than 10% of patients with CVCs receive any systemic prophylaxis. Although its general use cannot be recommended, low-dose warfarin may be a low-risk treatment in patients with good nutrition and adequate hepatic function. Clearly, additional studies are required to substantiate the prophylactic use of low-dose warfarin. Newer anticoagulant treatments, such as pentasaccharide and direct thrombin inhibitors, need to be explored to address this major medical problem.
The Molecular Perspective: Cytochrome c and Apoptosis
Authors: Goodsell David S. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Describe the structure and function of cytochrome c and its role in apoptosis and cancer.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at http://CME.TheOncologist.com
Highlights from the Tenth World Conference on Lung Cancer
Authors: Evans Tracey L. 
Published: August 2004

Abstract
Should adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC) be the standard of care? That question has been much debated since the presentation of results from the International Adjuvant Lung Cancer Trial (IALT) in May 2003 at the plenary session of the American Society of Clinical Oncology annual meeting. The IALT study showed a statistically significant survival advantage for patients treated with cisplatin-based adjuvant chemotherapy. The topic of adjuvant chemotherapy permeated the Tenth World Conference on Lung Cancer held from August 10–14, 2003 in Vancouver, Canada. Updated results of the IALT study were presented along with results from the Big Lung Trial from the United Kingdom and the Adjuvant Lung Project Italy trial, neither of which showed a significant survival benefit for adjuvant chemotherapy. How to put the IALT data into practice remains controversial, and leading lung cancer experts have not reached a consensus.
Platinum-based doublets that include a taxane, vinorelbine, or gemcitabine remain the standard of care for the first-line treatment of metastatic NSCLC. However, there may soon be a new option for second-line treatment. A randomized study of pemetrexed in the second-line setting found efficacy similar to that of docetaxel given every 3 weeks, with less toxicity.
Gefitinib was recently approved by the U.S. Food and Drug Administration for the treatment of advanced NSCLC following platinum-based chemotherapy and docetaxel. However, concerns have arisen about toxicity due to reports of interstitial pneumonitis from Japan. The observed incidence of interstitial pneumonitis from the data available to date is approximately 1%. Which patients derive the most benefit from gefitinib? It appears that lifetime nonsmokers and patients with bronchioloalveolar histology have the highest probability of disease response.
T-Cell Large Granular Lymphocyte Leukemia and Related Disorders
Authors: Rose Michal G. , Berliner Nancy 
Published: August 2004

AbstractLearning ObjectivesAfter completing this course, the reader will be able to:Discuss the clinical manifestations of large granular lymphocyte leukemia and related disorders, including their association with autoimmune conditions. Describe recent developments in the understanding of the pathogenesis of large granular lymphocyte leukemia. Explain the treatment approach to large granular lymphocyte leukemia and its related disorders.Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at http://CME.TheOncologist.comT-cell large granular lymphocyte (LGL) leukemia is a clonal proliferation of cytotoxic T cells, which causes neutropenia, anemia, and/or thrombocytopenia. This condition is often associated with autoimmune disorders, especially rheumatoid arthritis, and other lymphoproliferative disorders. The diagnosis is suggested by flow cytometry demonstrating an expansion of CD8+CD57+ T cells and is confirmed by T-cell receptor gene rearrangement studies. Mounting evidence suggests that LGL leukemia is a disorder of dysregulation of apoptosis through abnormalities in the Fas/Fas ligand pathway. In most patients, this is an indolent disorder, and significant improvement of cytopenias can be achieved with immunosuppressive agents such as steroids, methotrexate, cyclophosphamide, and cyclosporin A. This review provides a concise, up-to-date summary of LGL leukemia and the related, more aggressive, malignancies of cytotoxic T cells and natural killer cells.
Optimizing Treatment of Chronic Myeloid Leukemia: A Rational Approach
Authors: Stone Richard M. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Discuss the rationale for using imatinib as front-line therapy for chronic phase CML. Interpret the results of the phase III trial comparing imatinib with interferon-alfa plus Ara-C in chronic-phase CML. Evaluate various options for CML treatment including imatinib, oral chemotherapy, interferon-based approaches, and allogeneic stem cell transplantation.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Imatinib mesylate, a novel, molecularly targeted agent for the treatment of chronic myeloid leukemia (CML), has expanded the management options for this disease and provided a paradigm for the treatment of other cancers. Imatinib is a potent, specific inhibitor of BCR-ABL, the constitutively active protein tyrosine kinase critical to the pathogenesis of CML. A randomized, phase III comparison of imatinib with interferon-alfa plus cytarabine as initial treatment for newly diagnosed chronic-phase CML, which demonstrated significantly higher rates of disease response with less toxicity, better quality of life, and a significantly longer progression-free survival time, provided the most persuasive data supporting a major role for imatinib. Currently, allogeneic stem cell transplantation is the only treatment modality with long-term data demonstrating curative potential in CML. An option for less than half of CML patients and associated with substantial morbidity and mortality, transplantation may still be appropriate initial therapy for certain patients. Busulfan and hydroxyurea have no demonstrable effect on disease natural history. The interferon-plus-cytarabine combination can induce durable cytogenetic remissions and was previously the CML pharmacotherapy standard of care, but it is often poorly tolerated. Imatinib is now indicated as first-line therapy for CML in all phases.
Indications for Imatinib Mesylate Therapy and Clinical Management
Authors: Guilhot François 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Describe the mechanism of action (i.e., the molecular targets) of the anticancer drug imatinib mesylate. Explain how inhibition of these targets confers clinical benefits in specific human cancers. List the most common clinical side effects of imatinib treatment. Manage the side effects of imatinib treatment so as to allow optimal patient management.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at http://CME.TheOncologist.com
Imatinib mesylate (Gleevec®, Glivec®, formerly STI571; Novartis Pharma AG; Basel, Switzerland) is a rationally-designed, molecularly-specific oral anticancer agent that selectively inhibits several protein tyrosine kinases central to the pathogenesis of human cancer. It has demonstrated remarkable clinical efficacy in patients with chronic myeloid leukemia and malignant gastrointestinal stromal tumors. Treatment with imatinib is generally well tolerated, and the risk for severe adverse effects is low. Adverse effects most commonly include mild-to-moderate edema, nausea and vomiting, diarrhea, muscle cramps, and cutaneous reactions. Hepatic transaminase level elevations and myelosuppression occur less frequently and resolve with interruption of imatinib therapy. In general, the incidence and severity of adverse effects tend to correlate with imatinib dose and, in chronic myeloid leukemia patients, the phase of disease; but, patient age and other factors are also associated with some types of reactions. With prompt and appropriate intervention, adverse effects in imatinib-treated patients have proven to be manageable across the spectrum of severity, and they seldom require permanent cessation of therapy. Dose reduction is not usually necessary, and reduction to subtherapeutic levels is not recommended.
New Chemotherapeutic Advances in Pancreatic, Colorectal, and Gastric Cancers
Authors: Diaz-Rubio Eduardo 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Explain the need for more effective chemotherapy regimens for the treatment of advanced pancreatic, gastric, and colorectal cancer. Select the most appropriate treatment regimen in each of these categories based on the best available evidence. Identify the many new agents that target novel molecules in these cancers that are being explored in combination with conventional chemotherapy regimens.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Pancreatic, gastric, and colorectal cancers are major causes of morbidity and mortality worldwide. When curative surgical resection is not an option, these malignancies tend to respond very poorly to chemotherapy and carry a dismal prognosis. There is, therefore, an urgent need for novel treatment strategies for these cancers. Great strides have been made in colon cancer treatment with the recent introduction of several novel agents, including capecitabine, irinotecan, and oxaliplatin either alone or in combination regimens. Treatment of advanced colon cancer, however, remains essentially palliative, and treatment-related toxicity remains a significant problem. The treatment of advanced gastric and pancreatic cancer has also seen the introduction of new agents, such as gemcitabine and irinotecan; however, the impact of these agents on survival has been small, and toxicity continues to be a major obstacle. The search for new chemotherapeutic agents and treatment strategies will need to focus on improving outcomes and safety and tolerability profiles. To date, several new agents have shown promise, including pemetrexed, G17DT, bevacizumab, and other targeted agents. Further research into their optimal use either alone or in combination regimens should be a priority.
Intermittent Androgen Deprivation Therapy for Prostate Cancer
Authors: Rashid Mohammad H. , Chaudhary Uzair B. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Explain the utility of intermittent androgen deprivation therapy in the management of patients with prostate cancer. Describe the preclinical observations leading to the development of intermittent androgen deprivation therapy. Identify the limitations in using intermittent androgen deprivation therapy for prostate cancer.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Androgen deprivation therapy for prostate cancer is associated with several complications, including loss of libido, hot flashes, night sweats, psychological stress, osteoporosis, anemia, fatigue, loss of muscle mass, glucose intolerance, and changes in lipid profile. The natural history of prostate cancer while on such therapy is the attainment of an incurable androgen-independent state. Early diagnosis by prostate-specific antigen screening, longer life expectancies, and a penchant for immediate therapy pose a problem where clinicians have to balance the potential benefits of early hormonal therapy with the risks of development of these metabolic and psychological complications. Intermittent androgen deprivation offers clinicians a prospect to improve quality of life in patients with prostate cancer by harmonizing the benefits of androgen ablation with a reduction in treatment-related side effects and expenditure. In this review we discuss the challenges and opportunities of this mode of therapy and shed light on some of the underlying molecular mechanisms.
Advances in Chemoprevention of Head and Neck Cancer
Authors: Rhee John C. , Khuri Fadlo R. , Shin Dong M. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Describe the mechanism of carcinogenesis of head and neck cancer. Explain chemoprevention with retinoids and other chemopreventive compounds. Discuss the published data including phase II and phase III randomized trials.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Head and neck squamous cell carcinoma is a devastating disease with a poor outcome in advanced stages, accounting for approximately 3% of all malignancies, with an estimated 37,200 new cases and 11,000 deaths annually in the U.S. Second primary tumors are estimated to occur at an annual rate of 3%–10% and are significant threats to long-term survivors. Chemoprevention is an appealing strategy, and its success has been demonstrated in breast cancer and familial adenomatous polyposis. High-dose retinoids have been shown to be active against oral premalignant lesions and in prevention of second primary tumors in the head and neck. New targets include the epidermal growth factor receptor, cyclooxygenase-2, and other molecular targets. Challenges in future head and neck cancer chemoprevention investigations include achieving long-lasting efficacy with retinoids and/or new agents, and determining the optimal dose and duration of therapy while maintaining acceptable toxicities.