bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Use of Chemotherapy in Soft-Tissue Sarcomas
Authors: Spira Alexander I. , Ettinger David S. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:Identify the role of doxorubicin and ifosfamide in soft tissue sarcomas.Identify the role of newer agents in soft tissue sarcomas.Appreciate the role of adjuvant therapy in the management of soft tissue sarcomas.Appreciate the role of neoadjuvant chemotherapy and radiotherapy in the management of soft tissue sarcomas.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
The treatment of advanced soft-tissue sarcomas is often palliative, although a subset of patients may be cured or have a long disease-free interval. This paper reviews the historical data over 30 years of treatment that has led to the use of ifosfamide and doxorubicin as the mainstay in the treatment of metastatic disease. These treatments have a high toxicity, relative to other chemotherapeutic regimens, with median response durations on the order of months. Agents developed in the last few years, whose role in the treatment of sarcomas is still evolving, are discussed as well. Finally, we discuss the role of chemotherapy in combination with surgery and radiation in the adjuvant and neoadjuvant settings.
State-of-the-Art Treatment of Metastatic Hormone-Refractory Prostate Cancer
Authors: Goodin Susan , Rao Kamakshi V. , DiPaola Robert S. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:Identify agents which have shown activity in the treatment of hormone refractory prostate cancer (HRPC).Recognize the mechanisms of resistance to chemotherapy in HRPC, including genetic alterations commonly found in advanced disease.Recognize the development of novel approaches to the treatment of HRPC.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Initial therapy for advanced prostate cancer includes androgen ablation by surgical or medical castration. Still, nearly all men with metastases will progress to hormone-refractory prostate cancer (HRPC). Current U.S. Food and Drug Administration-approved agents for the treatment of HRPC include mitoxantrone and estramustine, although the vinca alkaloids and the taxanes have shown promising activity in single-agent phase II trials. Combinations of these agents induce a biochemical response in greater than 50% of patients, but the median duration of response is approximately 6 months. Overall survival of patients treated with these combinations is approximately 18-24 months. Studies are ongoing to develop novel therapies that target specific molecular pathways or mechanisms of chemotherapy resistance. Novel agents under development include growth factor receptor inhibitors, antisense oligonucleotides, bisphosphonates, and cell differentiating agents. Evaluation and incorporation of these agents into existing treatment regimens will guide us in the development of more active regimens in the treatment of HRPC.
Impact of Tumor Hypoxia and Anemia on Radiation Therapy Outcomes
Authors: Harrison Louis B. , Chadha Manjeet , Hill Richard J. , Hu Kenneth , Shasha Daniel 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:Discuss the prognostic significance of intratumoral hypoxia and low hemoglobin levels in patients receiving curative-intent radiation for head and neck or cervical cancer.Describe the potential relationship between anemia and intratumoral hypoxia in patients with solid tumors.List possible interventions for improving intratumoral oxygenation and radiosensitivity in the radiation oncology setting.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Local recurrence remains a major obstacle to achieving cure of many locally advanced solid tumors treated with definitive radiation therapy. The microenvironment of solid tumors is hypoxic compared with normal tissue, and this hypoxia is associated with decreased radiosensitivity. Recent preclinical data also suggest that intratumoral hypoxia, particularly in conjunction with an acid microenvironment, may be directly or indirectly mutagenic. Investigations of the prognostic significance of the pretreatment oxygenation status of tumors in patients with head and neck or cervical cancer have demonstrated that increased hypoxia, typically designated in these studies as pO2 levels below 2.5-10 mm Hg, is associated with decreased local tumor control and lower rates of disease-free and overall survival. Hypoxia-directed therapies in the radiation oncology setting include treatment using hyperbaric oxygen, fluosol infusion, carbogen breathing, and electron-affinic and hypoxic-cell sensitizers. These interventions have shown the potential to increase the effectiveness of curative-intent radiation therapy, demonstrating that the strategy of overcoming hypoxia may be a viable and important approach. Anemia is common in the cancer population and is suspected to contribute to intratumoral hypoxia. A review of the literature reveals that a low hemoglobin level before or during radiation therapy is an important risk factor for poor locoregional disease control and survival, implying that a strong correlation could exist between anemia and hypoxia (ultimately predicting for a poor outcome). While having a low hemoglobin level has been shown to be detrimental, it is unclear as to exactly what the threshold for “low” should be (studies in this area have used thresholds ranging from 9-14.5 g/dl). Optimal hemoglobin and pO2 thresholds for improving outcomes may vary across and within tumor types, and this is an area that clearly requires further evaluation. Nonetheless, the correction of anemia may be a worthwhile strategy for radiation oncologists to improve local control and survival.
Virtual Connections: Internet Health Care
Authors: Penson Richard T. , Benson Renee C. , Parles Karen , Chabner Bruce A. , Lynch Thomas J. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Understand the increasingly important contribution of the Internet to information and connection for staff and patients with cancer. Evaluate the limited evidence on medical misinformation, isolation, and the limits of the Internet. Learn the best available oncology Internet resources.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members.
The 20th century success of the Internet is now translating into changes in 21st century medical practice. The changes brought about by the Internet have at once facilitated and complicated the practice of medicine. Physicians and patients are challenged to take advantage of the increased opportunities afforded by Internet access while being mindful of its drawbacks and the limitations to virtual communication. The case of Karen Parles, one of the authors, is presented. Karen developed locally advanced lung cancer and used the Internet to research her diagnosis. She found the information on lung cancer limited and confusing, and, in response, developed a website devoted to empowering lung cancer patients in their search for information and support (http://www.lungcanceronline.org). Here we discuss issues surrounding patients' use of the Internet for health information and communication with health care providers. The value of information-seeking as a coping mechanism is debated, and concerns are raised regarding confidentiality of electronic communications and the logistics of physicians adopting e-mail as a mechanism for communicating with patients.
Metastatic Pancreatic Cancer: Emerging Strategies in Chemotherapy and Palliative Care
Authors: El Kamar Francois G. , Grossbard Michael L. , Kozuch Peter S. 
Published: August 2004

AbstractThis update is devoted to discussion of optimal supportive and palliative care of patients with pancreatic cancer. Approximately 33,000 new cases of pancreatic cancer are predicted for the U.S. in 2002. Because diagnosis and intervention occur late in the course of this disease, the vast majority of patients already have metastatic disease at the time of diagnosis. These tumors are relatively resistant to systemic chemotherapy, making pancreatic cancer the fourth leading cause of cancer-related death in the U.S. and the Western world. For these reasons, efforts at identifying and treating disease-related symptomatology are priorities. This update overviews symptom management, supportive care strategies, and both standard and emerging palliative chemotherapy options. The incorporation of molecularly targeted therapies into treatment of metastatic pancreatic cancer is reviewed as well. These strategies are of relevance to internists, gastroenterologists, oncologists, and other specialists who care for patients with pancreatic cancer.
Docetaxel, Cisplatin, 5-Fluorouracil (TPF)-Based Induction Chemotherapy for Head and Neck Cancer and the Case for Sequential, Combined-Modality Treatment
Authors: Haddad Robert , Tishler Roy B. , Norris Charles M. , Mahadevan Anand , Busse Paul , Wirth Lori , Goguen Laura A. , Sullivan Christopher A. , Costello Rosemary , Case Mary Ann , Posner Marshall R. 
Published: August 2004

Abstract
Since the publication of the Veterans Affairs study in the early 1990s, much has been learned regarding the role of chemotherapy, radiation therapy, and more importantly, the role of combined-modality treatment with chemoradiation in the therapy of locally advanced head and neck cancer. There continues to be widespread variation and controversy in the timing, schedule, and intensity of chemotherapy and chemoradiation. Herein, we present the various approaches currently used in the year 2003 with a specific emphasis on the role of sequential combined-modality therapy combining chemotherapy, chemoradiotherapy, and surgery in the treatment of these malignancies.
The Forgotten Myeloproliferative Disorder: Myeloid Metaplasia
Authors: Tefferi Ayalew 
Published: August 2004

AbstractLearning ObjectivesAfter completing this course, the reader will be able to:Derive a conceptual understanding of the classification as well as the pathogenesis of chronic myeloproliferative disorders with emphasis on myelofibrosis with myeloid metaplasia. Recognize how myelofibrosis with myeloid metaplasia is diagnosed and know what the differential diagnosis constitutes. Be familiar with current therapeutic options in myelofibrosis with myeloid metaplasia.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.comMyelofibrosis with myeloid metaplasia is a hematologic disorder currently classified with polycythemia vera and essential thrombocythemia as a chronic myeloproliferative disease. The median age at diagnosis is 60 years, and more than 90% of patients are diagnosed after age 40 years. Clinical manifestations include massive splenomegaly, progressive anemia, profound constitutional symptoms, and extramedullary hematopoiesis. The diagnosis is confirmed by bone marrow examination after other causes of myelofibrosis are ruled out. Median survival is 5 years and causes of death include leukemic transformation. Prognosis is adversely affected by the presence of anemia (hemoglobin &lt;10 g/dl), leukopenia or leukocytosis (white blood cells &gt;30,000/μl), circulating blasts, and hypercatabolic symptoms. Conventional treatment is palliative and does not improve survival. In this regard, androgen preparations, corticosteroids, and erythropoietin are useful for the treatment of disease-associated anemia. Symptomatic splenomegaly is best managed by cytoreductive therapy or surgical removal. Radiation therapy is most useful in the treatment of nonhepatosplenic extramedullary hematopoiesis. New treatment approaches include the use of thalidomide alone or in combination with prednisone and hematopoietic stem cell transplantation.
Docetaxel-Based Combined-Modality Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer
Authors: Scagliotti Giorgio V. , Turrisi Andrew T. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Offer a critical analysis of docetaxel radiotherapy clinical studies and provide background basic science support. Discuss dose/administration/timing information, as available, for docetaxel and radiotherapy, and provide a foundation for clinical use and a platform for further research. Explain the potential benefit and outline the toxicities of the combination as used in international studies.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
The cytotoxic agent docetaxel not only has proven activity in non-small cell lung cancer—when used alone or in combination—but is also a potent radiosensitizer, and improved treatments are needed in all stages of this disease. In patients with locoregionally advanced (stage III) disease, docetaxel has shown efficacy with manageable toxicities when used alone or in combination with a platinum compound in a sequential manner before localized radical radiotherapy/surgery. Presently, therapeutic gains appear to be maximized by the use of concurrent chemotherapy and irradiation. This review focuses on research with combinations of docetaxel with either cisplatin or carboplatin and radiotherapy. Overall response and survival rates to date provide data worth pursuing. From phase I data, weekly docetaxel at 20 mg/m2 plus cisplatin at 25 mg/m2 or carboplatin to an area under the concentration time curve of 2 mg/ml•min with concurrent radiotherapy to 60 Gy over 6 weeks appear to be suitable for phase II trials. Predominant toxicities are esophagitis and neutropenia, but a low frequency of pulmonary toxicity is reported. Induction, concurrent, and consolidation docetaxel-based chemoradiotherapy in potentially resectable disease are all being investigated. Future research could include the investigation of computed tomography/ positron emission tomography-derived target volume radiotherapy, dose-escalated therapy, and alternative fractionation schedules in combination with docetaxel-based cytotoxic chemotherapy.
Velcade®: U.S. FDA Approval for the Treatment of Multiple Myeloma Progressing on Prior Therapy
Authors: Kane Robert C. , Bross Peter F. , Farrell Ann T. , Pazdur Richard 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Discuss the rationale and requirements for accelerated cancer drug approval by the U.S. Food and Drug Administration (FDA). Identify the current indications for the use of a recently approved agent, bortezomib (Velcade®, PS-341), in the treatment of multiple myeloma. Describe the plans for the further clinical development of this agent as part of accelerated approval by the FDA. Explain the mechanism of action of bortezomib and its role in cancer treatment.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Bortezomib (formerly PS-341), a promising new drug for the treatment of multiple myeloma, recently received accelerated approval from the U.S. Food and Drug Administration (FDA) for the therapy of patients with progressive myeloma after previous treatment. Two phase II studies of bortezomib used the same schedule of twice-weekly i.v. dosing for the first 2 weeks of each 3-week cycle. In a randomized study of 54 patients, two doses were compared (1.0 and 1.3 mg/m2) and objective responses occurred at both dose levels (23% versus 35%), including one complete response in each arm. In the other phase II study, 202 heavily pretreated patients (median of six prior therapies) all received the same schedule at 1.3 mg/m2. Of 188 evaluable patients, complete responses occurred in five (3%) and partial responses occurred in 47 (25%). The median duration of response was 365 days. The most clinically relevant adverse events were asthenic conditions, nausea, vomiting, diarrhea, thrombocytopenia, and a peripheral neuropathy that often was painful. This report highlights the FDA analysis supporting the accelerated approval.
Topotecan Dosing Guidelines in Ovarian Cancer: Reduction and Management of Hematologic Toxicity
Authors: Armstrong Deborah K. 
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 ovarian cancer. List the risk factors for increased hematologic toxicity after topotecan therapy. Discuss topotecan dose determination and the management of hematologic toxicity in higher-risk ovarian cancer patients.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Topotecan dosing considerations and alternative dosing schedules to reduce and manage myelosuppression during the treatment of relapsed ovarian cancer were reviewed. The myelosuppression patterns from phase I, II, and III clinical trials were analyzed to evaluate the degree of hematologic toxicity and to determine risk factors predictive of myelosuppression. Additionally, recent publications of alternative topotecan doses and schedules were examined. Extent of prior therapy, prior platinum therapy (particularly carboplatin), advanced age, impaired renal function, and prior radiation therapy were identified as potential risk factors for greater hematologic toxicity after topotecan therapy. Reducing the starting topotecan dose to 1.0 or 1.25 mg/m2/day is recommended to reduce the incidence of severe myelosuppression in high-risk individuals receiving topotecan for 5 consecutive days. Hematopoietic growth factors, transfusion therapy, and schedule adjustments may also help manage myelosuppression. Alternative schedules of 3-day or weekly dosing appear to have less myelotoxicity and are currently under evaluation. The clinical aspects of topotecan-related myelosuppression and results from clinical trials indicate that the dose, and possibly the dosing schedule, of topotecan can be modified to reduce hematologic toxicity and improve tolerance without compromising efficacy. Prospective individualization of topotecan dosing may prevent or minimize dose-limiting myelosuppression and allow patients to achieve the maximum topotecan benefit by improving their ability to complete therapy with fewer treatment delays. Ongoing clinical trials evaluating alternative dosing schedules with superior hematologic tolerability may facilitate the inclusion of topotecan in combination regimens for patients with ovarian cancer. Proposed topotecan dosing guidelines to reduce and manage myelosuppression are outlined.
HER1/EGFR Targeting: Refining the Strategy
Authors: Pérez-Soler Román 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Differentiate between ligand-dependent and ligand-independent human epidermal growth factor receptor tyrosine kinase activation and initiation of signaling. Describe the site of action of tyrosine kinase inhibitors and explain how this might impact their therapeutic profiles. Discuss the influence of all aspects of clinical trial design on measurable outcomes, including dosing regimen, protocol, and patient selection.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Human epidermal growth factor receptor (EGFR), HER, targeting has formed the basis of extensive and growing drug development programs in various companies. However, receptor biology is often poorly explained and confusing. The HER family of four naturally occurring receptors and one tumor-specific mutant can activate signaling via a complex and sophisticated range of mechanisms, which we are only beginning to understand. HER1/EGFR downstream signaling can lead to tumor growth and development via a host of processes, including enhanced cellular proliferation, survival, and metastasis. A range of potential therapeutic targets exists within the HER signaling system, both inside and outside the cell. Monoclonal antibodies and tyrosine kinase inhibitors, acting extracellularly and intracellularly, respectively, comprise two classes of agents most advanced in clinical development or already available for use. Despite promising single-agent activity in chemotherapy-resistant patients with non-small cell lung cancer (NSCLC), disappointing results from two phase III trials of the tyrosine kinase inhibitor gefitinib in NSCLC have been of concern to some. However, many factors may have contributed to this outcome, and it is not necessarily predictive of the future usefulness of these agents. Patient characteristics, lack of patient selection, dosing schedule, and trial design may all have played roles. It is important to remember that intracellular targeting of HER is a relatively novel approach, and our knowledge of how best to optimize such treatment is still unfolding. More clinical experience is needed.
The Evolving Role of Epoetin Alfa in Cancer Therapy
Authors: Henry David H. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Describe the use of epoetin alfa in the prevention and treatment of anemia related to cancer and its treatment. Discuss ongoing clinical issues with epoetin alfa, including alternative dosing options and the benefits of early intervention for anemia. Identify additional nononcologic clinical applications for epoetin alfa currently under investigation.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Since its initial indication as hormone-replacement therapy in the anemia of chronic kidney disease, epoetin alfa has become a mainstay of therapy for chemotherapy-related anemia. Clinical studies have shown that epoetin alfa administered once weekly or three times weekly improves hemoglobin levels, decreases transfusion requirements, and improves quality of life independent of tumor response to chemotherapy. Ongoing research is now evaluating ways to improve the response rate to epoetin alfa, the potential benefits of alternative dosing regimens and early treatment intervention, and nonanemia-related indications (e.g., cognitive impairment, asthenia). In addition, scientists are exploring the role of epoetin alfa in preventing apoptosis and ischemic brain injury, as well as its activity in other nonerythroid tissues. Thus, the role of epoetin alfa is likely to expand in the cancer setting in the coming years.