bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognition and Management of Hereditary Breast Cancer Syndromes
Authors: Thull Darcy L. , Vogel Victor G.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Identify the most important clinical genetic syndromes that increase the risk of hereditary breast cancer. Describe surgical management options that reduce the risk of developing hereditary breast cancer. Outline the risks and benefits of using chemopreventative interventions in carriers of genetic mutations that increase the risk of hereditary breast cancer.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Clinicians should recognize the genetic syndromes that predispose to the development of breast cancer so that patients may be afforded the opportunity to have genetic testing to assist them and their family members in making medical management decisions. Approximately 80%–90% of hereditary breast cancer cases are caused by mutations in the BRCA1 and BRCA2 genes. Other important clinical genetic predispositions include Cowden syndrome, Li-Fraumeni syndrome, Peutz-Jeghers syndrome, and ataxia-telangiectasia. The key to identifying women who are at risk for a hereditary breast cancer lies in obtaining an adequate, three-generation family history, including ethnic background. For unaffected women, breast cancer risks can be estimated using the quantitative models of Gail and Claus, but there are limitations to these models. Other quantitative models predict the likelihood that a patient is carrying a mutated gene. Genetic testing is available at selected laboratories for each of the hereditary syndromes described, and there are three possible outcomes to testing. These outcomes and their management implications are described in detail. Clinical management options for women at high risk for breast cancer include surveillance, chemoprevention, and prophylactic surgery. Application of these principles can reduce morbidity in women with genetic predispositions to breast cancer.
Anemia in Stage II and III Breast Cancer Patients Treated With Adjuvant Doxorubicin and Cyclophosphamide Chemotherapy
Authors: Kirshner Jeffrey , Hatch Marianne , Hennessy Daniel D. , Fridman Moshe , Tannous Rima E.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Identify the prevalence and incidence of anemia in early-stage breast cancer patients and the proportion of patients untreated for anemia. Discuss the relationship between certain patient characteristics (i.e., age and prechemotherapy hemoglobin level) and the risk of developing moderate to severe anemia during chemotherapy. Explain how anemia may progress from cycle to cycle of chemotherapy and quantify the drop in hemoglobin levels for different groups of patients.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Purpose. The incidence and severity of prechemotherapy anemia and chemotherapy-induced anemia experienced by women treated with adjuvant doxorubicin and cyclophosphamide (AC) therapy for stage II and III breast cancer are described.

Patients and Methods. Medical charts of 310 breast cancer patients who received chemotherapy at eight oncology practices during 1997 through 2001 were reviewed in this historical case series study. Prechemotherapy anemia was defined as a baseline hemoglobin value <12 g/dl. An anemic event during chemotherapy (used to define chemotherapy-induced anemia) was defined as either a drop in hemoglobin level below the threshold (≤10 g/dl), the receipt of a blood transfusion(s), or treatment with epoetin alfa.

Results. Overall, 40.0% of patients experienced moderate to severe anemia (i.e., their hemoglobin levels dropped to <10 g/dl) and 31.3% (97/310) were anemic prechemotherapy. Of the patients with mild anemia prechemotherapy, 61.9% developed moderate to severe anemia during chemotherapy. Only 47.4% (46/97) of those patients received epoetin alfa therapy during chemotherapy. Of the patients with normal prechemotherapy hemoglobin levels (≥12 g/dl), 88.3% developed some degree of anemia (<12 g/dl) during chemotherapy and 27.7% (59/213) developed moderate to severe anemia (<10 g/dl). Anemic events were experienced by 41.8% (89/213) of the patients with normal prechemotherapy hemoglobin levels.

Conclusions. We conclude that a significant proportion (31.3%) of stage II and III breast cancer patients are anemic prechemotherapy and that the incidence of anemia increases substantially from prechemotherapy through the postchemotherapy period. This evidence appears to warrant earlier evaluation of anemia and an intervention in the prechemotherapy stage.
Ethical Conflict in Providing Informed Consent for Clinical Trials: A Problematic Example from the Gynecologic Cancer Research Community
Authors: Markman Maurie
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Describe the importance of the informed consent process in clinical trials. Discuss the implications of the randomized phase III trial of maintenance paclitaxel chemotherapy in advanced ovarian cancer. Explain the responsibilities of clinical investigators and clinicians to inform their patients of new results that may affect their willingness to participate in clinical trials.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

The principle of respect for patient autonomy and the importance of informed consent are well established in the conduct of clinical research. However, in actual clinical practice, how one applies this concept is not always clear. The provocative results of a randomized trial examining “consolidation/maintenance” therapy in women with advanced ovarian cancer who achieved a clinically defined complete response to primary chemotherapy have raised difficult issues for clinicians and clinical investigators regarding their obligations to provide patients with information that may interfere with the conduct of ongoing or future research studies.
Diagnosis and Treatment of Cholangiocarcinoma
Authors: Anderson Christopher D. , Wright Pinson C. , Berlin Jordan , Chari Ravi S.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Describe the current state-of-the-art treatment of cholangiocarcinoma including the current results of aggressive resection, adjuvant therapies, and neoadjuvant therapies. Outline the criteria for determining resectability. Discuss the roles of chemotherapies and radiation therapies in the palliative care of the patient with unresectable cholangiocarcinoma. Identify the roles of operative bypass and endoscopic or percutaneous stenting in the palliation of cholangiocarcinoma.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Cholangiocarcinoma presents a formidable diagnostic and treatment challenge. The majority of patients present with unresectable disease and have a survival of less than 12 months following diagnosis. Progress has been made by the appropriate selection of patients for treatment options including resection, with the routine use of more aggressive resections in order to achieve margin-negative resections. This has resulted in longer survival times for these patients. Neoadjuvant and adjuvant therapies have, for the most part, not improved survival in patients with this tumor, and new strategies are needed to improve this line of therapy. The prognosis for unresectable patients is poor, and palliative measures should be aimed at increasing quality of life first and increasing survival second.
The Role of Topotecan in the Treatment of Brain Metastases
Authors: Wong Eric T. , Berkenblit Anna
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Discuss the role of chemotherapy in the treatment of brain metastases. Identify the properties of topotecan that are conducive to treating patients with brain metastases. Discuss the investigation of single-agent topotecan and topotecan in combination with other chemotherapeutic agents or radiotherapy in the treatment of brain metastases.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Despite advances in the treatment of systemic malignancies, the prognosis for patients with brain metastases continues to be dismal. Because the majority of cytotoxic agents seem to be unable to penetrate the blood-brain barrier, the role of chemotherapy in the treatment of brain metastases remains controversial. However, growing amounts of both laboratory and clinical data suggest that a few of the newly developed cytotoxic agents can cross the blood-brain barrier and may have a role in the treatment of patients with brain metastases. Topotecan, a novel topoisomerase I inhibitor, freely crosses the blood-brain barrier and may be clinically effective in both the therapeutic and prophylactic settings in patients with brain metastases. Recent studies have demonstrated the antitumor activity of topotecan against brain metastases, with objective response rates ranging from 33%-63% in patients with various solid tumors. The antitumor response in the central nervous system was often greater and occurred more quickly than the systemic antitumor response to topotecan treatment. This result may be explained by the lack of exposure of brain metastases to previous cytotoxic agents, suggesting a role for topotecan in patients with brain metastases. Early studies have also suggested that topotecan, an apparent radiosensitizer, may be particularly effective in combination with radiotherapy, the current standard of care for patients with brain metastases. In addition, preliminary data suggest that topotecan in combination with temozolomide (another cytotoxic agent that can cross the blood-brain barrier) may have synergistic antitumor activity against brain metastases. This review summarizes the available preclinical and clinical evidence for the role of topotecan in the treatment of brain metastases and concludes with three case studies.
Complementary and Alternative Therapies for Cancer
Authors: Cassileth Barrie R. , Deng Gary
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Describe the differences between complementary and alternative therapies. List common complementary and alternative therapies used by cancer patients. Know where to access reliable information.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit atCME.TheOncologist.com

Many cancer patients use therapies promoted as literal alternatives to conventional medical care. Such “alternative” modalities are unproven or were studied and found worthless. These can be harmful. An even greater proportion of cancer patients uses “complementary” therapies along with mainstream cancer treatment. Most are helpful adjunctive approaches that control symptoms and enhance quality of life. This review describes alternative as well as complementary therapies commonly used today by cancer patients. Herbal remedies also are discussed. Evidence regarding the efficacy and safety of complementary/alternative medicine (CAM) is reviewed, and implications for oncologists are discussed. To encourage open communication of CAM use by patients, oncologists should be knowledgeable about the most popular remedies and know where to find reliable information for themselves and for their patients.
The Role of Selective Estrogen Receptor Modulators in the Prevention of Breast Cancer: Comparison of the Clinical Trials
Authors: Martino Silvana , Costantino Joseph , McNabb Michelle , Mershon John , Bryant Katherine , Powles Trevor , Secrest Roberta J.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Discuss the tamoxifen breast cancer prevention trials and the general risk-benefit profile of tamoxifen for breast cancer prevention. Compare and contrast the tamoxifen breast cancer chemoprevention trials with the ongoing raloxifene chemoprevention trials in terms of study design and baseline patient characteristics. Describe the limitations of the completed and ongoing tamoxifen and raloxifene breast cancer chemoprevention trials and the areas for future breast cancer chemoprevention research.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at http://CME.TheOncologist.com

The role of estrogen in the development of breast cancer is well recognized, and the use of selective estrogen receptor modulators (SERMs) to reduce breast cancer risk continues to be evaluated. Tamoxifen is the only SERM approved for the reduction of breast cancer incidence in women at high risk. This approval was based on results from the Breast Cancer Prevention Trial. Although initial results from the Royal Marsden Hospital tamoxifen trial and Italian Tamoxifen Prevention Study did not show a similar overall effect of tamoxifen, recent updates from these two trials and initial results from the International Breast Cancer Intervention Study are consistent with a risk reduction effect of tamoxifen for estrogen-receptor-positive breast cancer.

Raloxifene, approved for the prevention and treatment of postmenopausal osteoporosis, is another SERM being evaluated for breast cancer risk reduction. The recently completed Continuing Outcomes Relevant to Evista® trial and the Raloxifene Use for The Heart trial, have breast cancer risk reduction as a primary end point. A third, ongoing trial, the Study of Tamoxifen and Raloxifene trial, is evaluating the relative efficacy and adverse event profile of these two agents in a population at high risk. The study populations of these raloxifene breast cancer prevention trials and the four tamoxifen prevention trials are quite diverse in terms of breast cancer risk. Completion of these trials will provide important information about the occurrence of invasive breast cancer in postmenopausal women and the efficacy of raloxifene for breast cancer risk reduction.
Aromatase Inhibitors for Breast Cancer in Postmenopausal Women
Authors: Campos Susana M.
Published: August 2004

Third-generation aromatase inhibitors are potent inhibitors of the aromatase enzyme, which catalyzes the last step in estrogen biosynthesis. These agents are active against breast cancer in hormone-naïve postmenopausal women and in women who have experienced failure of tamoxifen or failure of tamoxifen plus other hormonal therapy. There are two types of aromatase inhibitors, irreversible steroidal activators (e.g., exemestane) and reversible nonsteroidal imidazole-based inhibitors (e.g., anastrozole, letrozole). Recent data suggest that some women who experience failure of one type of aromatase inhibitor can subsequently derive benefit from the other type. The reason for this lack of cross-resistance is unknown. This finding of non-cross-resistance between steroidal aromatase activators and nonsteroidal aromatase inhibitors offers the opportunity to increase the number of lines of hormone therapy before making the inevitable switch to more toxic chemotherapy, thus potentially improving quality of life for postmenopausal women with advanced disease.

Data from postmenopausal women with advanced disease suggest that steroidal and nonsteroidal aromatase inhibitors have similar tolerability profiles; however, emerging data suggest that there may be differences in their effects on end organs, which may become evident with longer term use, such as in the adjuvant or prevention settings. Steroidal agents appear to have beneficial effects on lipid and bone metabolism, whereas nonsteroidal agents may have neutral or unfavorable effects. These differences may be attributed to the androgenic effects of steroidal agents; clinical trials are currently under way to confirm these suspicions.
Multiple Management Modalities in Esophageal Cancer: Epidemiology, Presentation and Progression, Work-up, and Surgical Approaches
Authors: Koshy Mary , Esiashvilli Natia , Landry Jerome C. , Thomas Charles R. , Matthews Richard H.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Describe the epidemiology, work-up, and staging of esophageal cancer. Identify the disease presentation, progression, and prognostic factors for esophageal cancer. Discuss the surgical approach and management of esophageal cancer.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at http://CME.TheOncologist.com

Annually, approximately 13,200 people in the U.S. are diagnosed with esophageal cancer and 12,500 die of this malignancy. Of new cases, 9,900 occur in men and 3,300 occur in women. In part I of this two-part series, we explore the epidemiology, presentation and progression, work-up, and surgical approaches for esophageal cancer. In the 1960s, squamous cell cancers made up greater than 90% of all esophageal tumors. The incidence of esophageal adenocarcinomas has risen considerably over the past two decades, such that they are now more prevalent than squamous cell cancer in the western hemisphere. Despite advances in therapeutic modalities for this disease, half the patients are incurable at presentation, and overall survival after diagnosis is grim. Evolving knowledge regarding the etiology of esophageal carcinoma may lead to better preventive methods and treatment options for early stage superficial cancers of the esophagus. The use of endoscopic ultrasound and the developing role of positron emission tomography have led to better diagnostic accuracy in this disease. For years, the standard of care for esophageal cancer has been surgery; there are several variants of the surgical approach. We will discuss combined modality approaches in part II of this series.
Multiple Management Modalities in Esophageal Cancer: Combined Modality Management Approaches
Authors: Koshy Mary , Esiashvilli Natia , Landry Jerome C. , Thomas Charles R. , Matthews Richard H.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Outline the relative merits of definitive radiation alone or as a preoperative or postoperative treatment for esophageal cancer versus combined chemoradiation in these settings. Discuss the limitations of our understanding of the radiation dose-response relationship in esophageal cancer. Appreciate the merits of chemoradiation as definitive treatment for esophageal cancer versus its use as an adjuvant to surgery.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at http://CME.TheOncologist.com

The overall success rate nationally in treating esophageal carcinomas remains poor, with over 90% of patients succumbing to the disease. In part I of this two-part series, we explored epidemiology, presentation and progression, work-up, and surgical approaches. In part II, we explore the promising suggestions of integrating chemotherapy and radiation therapy into the multimodal management of esophageal cancers.

Alternative approaches to resection alone have been sought because of the overall poor survival rates of esophageal cancer patients, with failures occurring both local-regionally and distantly. Concomitant chemotherapy and radiation therapy (XRT) have been shown, by randomized trial, to be more effective than XRT alone in treating unresectable esophageal cancers and also have shown promise as a neoadjuvant treatment when combined with surgery in the multimodal treatment of this disease. Various studies have also addressed issues such as preoperative chemotherapy, radiation dose escalation, chemotherapy/XRT as a definitive treatment versus use as a surgical adjuvant, and alternative chemotherapy regimens. There are suggestions of some progress, but this remains a difficult problem area in which management is continuing to evolve.
Bexxar®: Novel Radioimmunotherapy for the Treatment of Low-Grade and Transformed Low-Grade Non-Hodgkin's Lymphoma
Authors: Vose Julie M.
Published: August 2004

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

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

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

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 (>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

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

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

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

Learning Objectives

After 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.com

T-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

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

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

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

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.

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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

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.

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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.
Safety and Convenience of a 15-Minute Infusion of Zoledronic Acid
Authors: Berenson James , Hirschberg Raimund
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Describe the effects of bisphosphonates on bone metabolism in patients with metastatic bone disease. Explain the ability of intravenous bisphosphonates to reduce skeletal complications in patients with metastatic bone disease. Identify differences among the different bisphosphonates in their efficacies at reversing hypercalcemia of malignancy.

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Skeletal morbidity, including hypercalcemia of malignancy (HCM), places a severe burden on patients with advanced cancers. Bisphosphonates effectively correct HCM and reduce skeletal morbidity in patients with bone metastases. However, with the widespread use of bisphosphonates, the safety and convenience of therapy are emerging concerns. The delivery of effective doses of early bisphosphonates required a lengthy 24-hour i.v. infusion protocol because of renal tolerability issues. The introduction of more potent bisphosphonates with superior tolerability profiles has allowed therapy to be safely delivered via shorter i.v. infusions. Intravenous therapy with etidronate, clodronate, pamidronate, ibandronate, and zoledronic acid has been used to treat HCM and skeletal complications in cancer patients. Of these therapies, zoledronic acid (which can be safely administered via a 15-minute i.v. infusion) is the most convenient and effective and has demonstrated an excellent safety profile with long-term use. Zoledronic acid has also received the broadest regulatory approval of any bisphosphonate and can be used to treat HCM or bone lesions secondary to multiple myeloma and a wide variety of solid tumors, including breast, prostate, and lung cancers. In addition to the patient preference for shorter infusion times, the 15-minute i.v. infusion protocol of zoledronic acid can provide benefits for infusion centers by potentially increasing patient throughput.
Too Old to Care?
Authors: Penson Richard T. , Daniels Kristy J. , Lynch Thomas J.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Discuss the competing issues in the use of cytotoxic chemotherapy in older patients. Identify the intrinsic biases in evaluating the elderly. Explain how to inform patients in the face of uncertainty.

Access and take the CME test online and receive 1 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 (http://www.theschwartzcenter.org/rounds.asp). The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient and 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.

Ageism is a pervasive problem throughout society. It is rooted in language, attitudes, beliefs, behaviors, and policies. Aging profoundly influences physiology, challenging the medical community to accommodate but not discriminate. The elderly are at an increased risk of disease and disability. Sixty percent of cancer occurs in people aged 65 and older, and the population is aging. The treatment of cancer in the elderly is complicated by comorbidities and other physiological factors, particularly renal, bone marrow, and metabolic reserve. Caregivers have to treat patients in a manner that optimizes treatment and avoids anticipated harm. However, the caregiver is often faced with situations where they must balance their personal beliefs, professional values, and knowledge of medicine with their patients' preferences and needs. Discussion in the Rounds focused on age bias, drug toxicity, life prolongation, and symptom relief, with the role of the caregiver, and the relationship to the patient, being pivotal.
The Molecular Perspective: Nicotine and Nitrosamines
Authors: Goodsell David S.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Describe the role of nitrosamines in cancer.

Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com