bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Targets of Arsenic Trioxide in Malignant Cells
Authors: Miller Wilson H.
Published: August 2004

Learning Objectives

After taking all of the CME courses in this supplement the reader will be able to: Describe the basic biology of various leukemias, multiple myeloma, and myelodysplastic syndrome (MDS).Discuss new targeted treatment strategies for hematologic malignancies.Understand the rationale for the use of nontraditional cytotoxic agents such as arsenic trioxide in the treatment of hematologic malignancies.Examine the role of arsenic trioxide and other novel agents in early-versus accelerated-stage hematologic disease.Discuss the preclinical and clinical efficacy of arsenic trioxide and various agents in treating acute promyelocytic leukemia, MDS, and multiple myeloma.

Access CME test online and receive one hour category 1 credit at CME.TheOncologist.com

Arsenic trioxide (As2O3; ATO) has considerable efficacy in the treatment of relapsed acute promyelocytic leukemia (APL), inducing partial differentiation and promoting apoptosis of malignant promyelocytes. Although initial studies focused on the role of the characteristic APL fusion protein, PML-RARα, in mediating response to ATO, subsequent investigations have revealed that ATO acts on numerous intracellular targets. ATO broadly affects signal transduction pathways and causes a wide range of alterations leading to apoptosis. Key mediators of sensitivity to ATO-induced apoptosis include intracellular glutathione and hydrogen peroxide (H2O2). The loss of inner mitochondrial membrane potential is also an important step in ATO-mediated cell killing. Cellular and physiologic pathways affected by ATO provide some clues as to the mechanisms for the biologic effects of ATO. Recent research has shown that hematologic cancers other than APL and solid tumors derived from several tissue types may be responsive to monotherapy or combination therapy with ATO. A better understanding of the mechanisms of action of ATO may help guide the use of ATO for the treatment of a wide variety of malignancies and allow its potential in cancer therapy to be fully realized.
Nontraditional Cytotoxic Therapies for Relapsed/Refractory Multiple Myeloma
Authors: Hussein Mohamad A.
Published: August 2004

Learning Objectives

After taking all of the CME courses in this supplement the reader will be able to:

Describe the basic biology of various leukemias, multiple myeloma, and myelodysplastic syndrome (MDS). Discuss new targeted treatment strategies for hematologic malignancies. Understand the rationale for the use of nontraditional cytotoxic agents such as arsenic trioxide in the treatment of hematologic malignancies. Examine the role of arsenic trioxide and other novel agents in early-versus accelerated-stage hematologic disease. Discuss the preclinical and clinical efficacy of arsenic trioxide and various agents in treating acute promyelocytic leukemia, MDS, and multiple myeloma.

Access CME test online and receive one hour category 1 credit at CME.TheOncologist.com

Multiple myeloma remains an incurable disease, with median survival rates of 4-6 years even with aggressive, high-dose chemotherapy, bone marrow transplantation, and intensive supportive care. Additionally, multiple myeloma is primarily a disease of the elderly, many of whom cannot tolerate aggressive chemotherapy. Thus, newer treatments with good safety profiles are needed to improve the quality of responses and, hopefully, to translate into prolonged progression and overall survival. The pathophysiology of multiple myeloma is complex, involving many pathways and interactions among cytokines, adhesion molecules, angiogenesis, and mechanisms of resistance, which, taken together, provide multiple targets for novel therapeutic modalities. Agents currently under investigation for treating multiple myeloma include thalidomide and its successors, PS-341, and arsenic trioxide. Thalidomide and immunomodulatory drugs both exhibit activity against multiple myeloma by affecting different levels of the immune system. PS-341 is a proteasome inhibitor that halts the cell cycle, resulting in apoptosis; it also inhibits a key transcription factor and may have antiangiogenic activity. Arsenic trioxide activates multicellular mechanisms to induce apoptosis, inhibit angiogenesis, and stimulate immune responses. Preclinical and early clinical data suggest that combination regimens should be pursued, given the different mechanisms of action of these compounds on the immune system and their non-overlapping toxicities at low dosages.
A Staff Dialogue on Aggressive Palliative Treatment Demanded by a Terminally Ill Patient: Psychosocial Issues Faced by Patients, Their Families, and Caregivers
Authors: Lintz Kathleen C. , Penson Richard T. , Cassem Ned , Harmon David C. , Chabner Bruce A. , Lynch Thomas J.
Published: August 2004

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 which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum during which caregivers discuss a specific cancer patient, reflect on the important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from their fellow staff members.

In this article, the case presentation and verbatim dialogue from the rounds are discussed with an emphasis on staff psychosocial issues. The case presented was of a 32-year-old man, who developed small cell osteosarcoma and was treated at MGH. He died after undergoing multiple courses of relatively ineffective chemotherapy. The case is made all the more poignant because of the pleasures, hopes, and stresses of having a child late in the course of his illness. Staff identified closely, both with him and his family, and their concern for him brought joy and meaning to their work, yet this complicated their ability to deal with his impending death. They felt that his unwillingness to admit defeat prevented them from saying goodbye to someone whom they loved and admired. Despite this, staff recognized that, ultimately, the patient's emotional needs and wishes had to be respected as a first priority and that constructive closure can be worked toward, if not achieved. In such situations, it is vital to have a colleague support system and a forum for discussion of such issues in order to defuse distress and reassure staff that they are doing all that can be done as professionals and caregivers.
A Staff Dialogue on Do Not Resuscitate Orders: Psychosocial Issues Faced by Patients, Their Families, and Caregivers
Authors: O'Shea Elizabeth M. , Penson Richard T. , Stern Theodore A. , Younger Jerry , Chabner Bruce A. , Lynch Thomas J.
Published: August 2004

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 non-profit organization dedicated to supporting and advancing compassionate health care delivery which 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 following case of a woman who developed lymphoma was discussed at the July and August, 1997 Schwartz Center Rounds. There were considerable delays and uncertainties in the diagnosis, which was followed by an unpredictably chaotic clinical course. Although she had made it clear to her doctor that she did not want “heroic measures,” she had unexpectedly rallied so many times that her son and her husband wanted her doctors to do everything possible to keep her alive, including the performance of cardiopulmonary resuscitation (CPR). The clinical benefit of CPR in the event of cardiac arrest in those with cancer is discussed, as are do not resuscitate (DNR) orders, living wills, and health care proxies. In addition, the issues that surround DNR status, including who should discuss DNR status with a patient, and how and when it should be discussed, are reviewed. Staff raised concerns about the effect of discussing DNR status on the doctor-patient relationship, and wondered whether writing DNR orders adversely affects the care of patients.
A Staff Dialogue on a Socially Distanced Patient: Psychosocial Issues Faced by Patients, Their Families, and Caregivers
Authors: Goodman Annekathryn , Penson Richard T. , Blatman Robert , McIntyre James , Gioiella Marie Elena , Chabner Bruce A. , Lynch Thomas J.
Published: August 2004

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 non-profit organization dedicated to supporting and advancing compassionate health care delivery, which 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 following case of an HIV-positive woman who was diagnosed with cervical cancer during a twin pregnancy was discussed at the May, 1999 Schwartz Center Rounds. The patient was in drug rehabilitation having been dependant on crack cocaine, with a past history of syphilis and gonorrhea. She was single and her other children were in foster care. Initially she was suspicious and non-compliant. A plan was negotiated to biopsy the cervical lesion after cesarean section and with confirmation of malignancy she underwent radical surgery and subsequently radiotherapy. Despite the almost insurmountable social and educational distance between her and her caregivers, they managed to bond and facilitate care. Although there were compromises with which staff were uncomfortable, the relationship was maintained and continues.
Reality Testing in Cancer Treatment: The Phase I Trial of Endostatin
Authors: Ryan David P. , Penson Richard T. , Ahmed Sabrina , Chabner Bruce A. , Lynch Thomas J.
Published: August 2004

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 non-profit organization dedicated to supporting and advancing compassionate health care delivery which 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 September 1999 Schwartz Center Rounds addressed the growing attention around the phase I trial of Endostatin™. Endostatin represents a new treatment paradigm. It is an antiangiogenic protein, an endogenous fragment of collagen XVIII. In an attempt to ensure a fair allocation of a very limited number of treatment slots in this classical phase I trial, a lottery was established. More than 1,400 patients enrolled within 2 days of the lottery, all vying for three places in the first cohort. Two contrasting cases are presented, each a potentially eligible patient. The discussion focuses on the dilemma presented by patients desperate for an unproven treatment and the responsibility of staff to explain and support without compounding the hype or suffocating the hope.
A Staff Dialogue on Phase I Trials: Psychosocial Issues Faced by Patients, Their Families, and Caregivers
Authors: Lintz Kathleen C. , Penson Richard T. , Chabner Bruce A. , Mack Sally , Lynch Thomas J.
Published: August 2004

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded The Kenneth B. Schwartz Center to be housed at Massachusetts General Hospital (MGH). He created this center to advance the hopes, goals, and ideas expressed in his article, “A Patient's Story,” published in the July 16, 1995 issue of the Boston Globe Magazine. The Schwartz Center is a non-profit organization dedicated to strengthening the relationship between patients and caregivers and to supporting and advancing “compassionate health care delivery in which caregivers, patients, and their families relate meaningfully to one another in a way that provides hope to the patient, support to caregivers, and sustenance to the healing process.” One of the Center's major projects is the sponsoring of the Schwartz Center Rounds, a monthly, multidisciplinary forum in which caregivers discuss a specific cancer patient and the important psychosocial issues faced by the patient, family, and caregivers. The forum allows caregivers to reflect on their experiences with patients and to gain support and insight from fellow staff members.

The following case discussion was addressed at the January 1998 Schwartz Center Rounds. In this article, the case will be presented, followed by verbatim dialogue from the Rounds and a subsequent discussion of the relevant issues with emphasis on staff psychosocial issues.

J.T. was a 43-year-old man who developed adenocarcinoma of the lung and was treated at MGH. He died while participating in a phase I trial, resulting in marked frustration and distress among his caregivers. Staff questioned whether cancer patients entering phase I trials and their families receive unbiased information about the possible risks and benefits of the trial. They were also concerned about whether or not patients and their families really understand the physical and emotional risks of a trial. Moreover, they addressed whether patients are presented with alternatives to enrolling in a phase I trial, such as palliative care. Despite all these concerns, caregivers are reconciled to the belief that patients do value the opportunity to participate in phase I trials, in that they can contribute hope and meaning to other patients' struggles with cancer.
Cytotoxic Agents in the Era of Molecular Targets and Genomics
Authors: Chabner Bruce A.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to: Identify single nucleotide polymorphisms.Explain how they could influence drug response and toxicity in cancer patients.Explain how the DNA repair capability of tumor cells affects their response to ET-743 and other cancer drugs.

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

Cancer treatment is evolving due to the development of molecularly targeted agents and the utilization of pharmacogenomics and pharmacogenetics to identify patients who are at an increased risk for toxicity or may be uniquely responsive to cytotoxic therapies. By identifying polymorphisms in the human genome that confer changes in the ability to metabolize or activate cancer agents, a more patient-specific treatment approach can be initiated. Molecularly targeted therapies such as PS-341, flavopiridol, Iressa, and anti-vascular endothelial growth factor antibodies may help to overcome resistance to cytotoxic therapies by lowering the apoptotic threshold and increasing cytotoxicity. Using molecularly targeted agents in combination with traditional cytotoxic agents may increase the percentage of patients who achieve disease stabilization and prolonged survival. With the development of genetic tools and genotyping of tumor and patient prior to initiating treatment, antitumor efficacy may be increased with a substantial reduction in toxicity.
Vascular Endothelial Growth Factor: Regulation in the Mouse Skin Carcinogenesis Model and Use in Antiangiogenesis Cancer Therapy
Authors: Conti Claudio J.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to: Describe mechanisms of tumor neovascularization.Identify possible targets for cancer therapy in the biologic pathways that control angiogenesis.Identify some of the drugs that are presently used in preclinical or clinical trials, as well as their targets.

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

Of the various mechanisms responsible for tumor neovascularization, the angiogenesis process, in particular vascular endothelial growth factor (VEGF), is described here as a target for cancer therapy. While hypoxia is a trigger of tumor angiogenesis, various alterations in oncogenes and tumor suppressor genes also have been reported to induce VEGF expression in tumors. The regulation of VEGF has been investigated in chemically induced mouse squamous cell carcinoma of the skin. In this cancer model, VEGF expression appears to be dependent on ras oncogene activation as well as the epidermal growth factor receptor. Thus, in addition to VEGF, oncogene signaling pathways may be relevant targets in antiangiogenesis cancer therapies.

The central role of VEGF in angiogenesis has led to the development of several drugs targeting the pathway of this growth factor. The present paper provides an overview of these drugs and their stage of development. In the near future, clinical trials using anti-VEGF drugs and other antiangiogenic agents, such as endostatin and angiostatin, will yield valuable information about their potential for cancer therapy.
ZD1839 (Iressa™): For More Than Just Non-Small Cell Lung Cancer
Authors: Ranson Malcolm
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:Recognize the basic biology and importance of the erbB family of growth factor receptors.Explain the current status of clinical development of ZD1839 in solid tumors other than non-small cell lung cancer (NSCLC).Appreciate some of the future directions for clinical research for this class of anti-tumor agent.

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

ZD1839 (Iressa™) is an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor that blocks signal transduction pathways involved in cell proliferation. Preclinical studies demonstrated that ZD1839 is a promising agent for the treatment of a wide range of tumors and has additive-to-synergistic effects when combined with radiation or chemotherapy in various cell lines and xenografts. Phase I clinical trials have reported that ZD1839 has acceptable tolerability and antitumor activity. In addition to non-small cell lung cancer, phase II/III studies are currently investigating ZD1839 as monotherapy or in combination therapy against prostate, breast, head and neck, gastric, and colorectal tumors.
ZD1839 (Iressa™): What's in It for the Patient?
Authors: Natale Ronald B. , Zaretsky Susan L.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:Identify the available survey instruments for measuring the quality of life (QOL) of patients with lung cancer.Appreciate the importance of symptom management to cancer patients.Learn how QOL measurements are being assessed in clinical trials in lung cancer.Recognize the global burden of lung cancer.

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

Although cytotoxic chemotherapy has had a significant impact on the treatment of some malignancies, its impact against most solid tumors is limited. This is especially true in the case of non-small cell lung cancer (NSCLC) in which about 90% of patients ultimately die from metastatic disease. Although chemotherapy has produced modest improvements in response rates and survival in a subset of patients with advanced NSCLC, its primary objective remains to provide palliation of disabling disease-related symptoms. It is hoped that the introduction of new, rationally designed anticancer agents, with greater specificity and less toxicity, will improve the outcome for patients with a range of tumor types, including NSCLC.

ZD1839 (Iressa™) is the first of a new class of epidermal growth factor receptor tyrosine kinase inhibitors. The results of two large phase II trials have shown that ZD1839 provides clinically significant symptom relief for many patients with extensively pretreated advanced NSCLC. Moreover, this improvement in disease-related symptoms correlated with improved survival and tumor response. ZD1839 also had an acceptable tolerability profile: most drug-related adverse events were mild and reversible and quite different from those typically associated with cytotoxic agents. Some patients also experienced improved quality of life, particularly those with a partial response or stable disease. Thus, ZD1839 offers a new treatment option providing meaningful symptom relief for many patients with advanced NSCLC.
Epidermal Growth Factor Receptor Dependence in Human Tumors: More Than Just Expression?
Authors: Arteaga Carlos L.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:Describe the current limitations in measuring levels of EGR receptor (EGFR) expression in tissues.Identify the molecular pathways for signal transduction induced by EGFR activation.Identify the level of expression of EGF in different tumor types.

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

The epidermal growth factor receptor (EGFR) is a rational target for antitumor strategies. EGFR signaling causes increased proliferation, decreased apoptosis, and enhanced tumor cell motility and neo-angiogenesis. The EGFR is expressed or highly expressed in a variety of human tumors of epithelial origin. ZD1839 (Iressa™) is an orally active, selective EGFR tyrosine kinase inhibitor, which blocks signal transduction pathways implicated in proliferation and survival of cancer cells.

The lack of a consistent method of evaluating levels of EGFR has caused a disparity in reports of the EGFR as a prognostic factor; however, for some tumors, EGFR is a strong prognostic indicator associated with more aggressive disease and reduced survival. So far, no clear association between EGFR levels and response to EGFR-targeted agents has been found. Preclinical studies with ZD1839 have noted a relationship between the two in some cases, but not others.

EGFR signaling may be increased by a number of mechanisms in addition to high expression levels of EGFR, including receptor mutations, heterodimerization with other members of this receptor family such as HER2 (erbB2), increased expression of (autocrine/ paracrine) ligands, and alterations in molecules that control receptor signaling output. Each of these components could be assessed to give an indication of the magnitude of EGFR signal amplification. Evaluation of signaling components downstream from EGFR should provide information on the activation of the EGFR pathway.

Until EGFR-based assays predictive of a response to receptor-targeted therapies are available, there is no clear justification for stratifying patients by EGFR status or excluding patients with low EGFR levels from trials with ZD1839 or other EGFR inhibitors.
ZD1839 (Iressa™) in Non-Small Cell Lung Cancer
Authors: Herbst Roy S. , Kies Merrill S.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:Identify the current status of Phase I, II, and III trials of ZD1839 in non-small cell lung cancer (NSCLC).Describe the clinical development plan for ZD1839 in second line, adjuvant (maintenance), and prevention in patients with NSCLC.Identify treatment options for patients with NSCLC.

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

Despite the advent of cisplatin-based combination chemotherapy for advanced non-small cell lung cancer (NSCLC), the prognosis for this patient population remains poor. Novel biologically targeted agents currently in development have the potential for greater efficacy against NSCLC, and possibly less toxicity than is associated with conventional cytotoxic chemotherapy. The epidermal growth factor receptor (EGFR) is recognized as a potentially useful target, and the small molecule, orally active EGFR-tyrosine kinase inhibitor ZD1839 (Iressa™) is currently the furthest along in clinical development of the anti-EGFR agents. This review summarizes the currently available clinical data on the use of ZD1839 in the treatment of NSCLC.
Relapsed Ovarian Cancer: Challenges and Management Strategies for a Chronic Disease
Authors: Armstrong Deborah K.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:Better appreciate the challenges faced in managing treatment of patients with ovarian cancer.Describe the factors that impact on the design of long-term treatment strategies for patients with relapsed ovarian cancer.Describe important disease management issues, including when to initiate treatment, which treatments to consider and why, and patient education.

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

Advances in the treatment and early detection of ovarian cancer have led to gains in 5-year survival rates, with 52% of women diagnosed between 1992 and 1997 surviving 5 years or longer, compared with 41% of women diagnosed between 1983 and 1985. Although approximately 10%-15% of patients achieve and maintain complete responses to therapy, the remaining patients have persistent disease or eventually relapse. These patients will generally undergo a series of treatments, each associated with progressively shorter treatment-free intervals. Nevertheless, median survival of patients with recurrent ovarian cancer ranges from 12-24 months, demonstrating the chronic natural history of the disease. Advances in the treatment of ovarian cancer over the past decade have led to these improvements and have prompted oncologists to now view the management of patients with ovarian cancer as an ongoing, long-term challenge. This shift in approach has raised important new questions regarding patient management, including the need to define trigger points for initiating or changing treatment (e.g., sequential increases in serum cancer antigen 125 levels, appearance of symptoms, or cumulative toxicities), anticipation of impending treatment decision points, recognition that the overtreatment of patients early in the disease process may adversely affect future treatment opportunities, and a renewed emphasis on patient education and participation in decision-making. This review will discuss these important patient management issues and will conclude with case studies illustrating two distinct treatment strategies (planning and sequencing) for the long-term management of patients with ovarian cancer.
Alternate Dosing Schedules for Topotecan in the Treatment of Recurrent Ovarian Cancer
Authors: Morris Robert , Munkarah Adnan
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:Identify the rationale for exploring alternative dosing schedules for topotecan.Identify which alternative schedules are being explored and have the most promise.Identify the tolerance and antitumor activity of alternative dosing regimens for topotecan.

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

Topotecan has demonstrated efficacy in the treatment of both platinum-sensitive and platinum-resistant recurrent ovarian cancer. However, the optimal dosing for topotecan has not been established. The standard dosing regimen is 1.5 mg/m2/day on days 1-5 of a 21-day cycle, with response rates ranging from 13%-33%. Although the resulting hematologic toxicities are reversible and noncumulative, this schedule is associated with significant myelosuppression. Ongoing clinical phase I and II trials have evaluated alternative dosing schedules such as the 21-day 24-hour continuous intravenous (c.i.v.), the 3-day i.v. bolus, the weekly 72-hour c.i.v., the weekly 24-hour c.i.v., and the weekly bolus i.v. regimens. Prolonged exposure to topotecan has been shown to increase the efficacy of topotecan, whereas shorter regimens decrease exposure to the drug and therefore decrease toxicity. Preliminary studies investigating the weekly bolus i.v. regimen have demonstrated response rates comparable with those achieved with the standard dosing regimen, with a lower frequency of severe toxicity. Although randomized, controlled comparative trials are necessary to determine relative efficacy, results from studies utilizing other alternative regimens are less encouraging, especially for lower-risk patients with platinum-sensitive ovarian cancer who are likely to tolerate higher doses of topotecan. Optimizing the dosing regimen will also increase the quality of life for the patient through increased efficacy, decreased toxicity, and increased convenience of administration. Continued investigation of the weekly i.v. bolus is needed to fully elucidate the contribution of this regimen to the current armamentarium used in the treatment of patients with relapsed ovarian cancer.
Update on the Role of Topotecan in the Treatment of Recurrent Ovarian Cancer
Authors: Herzog Thomas J.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to: Describe the latest literature on the use of topotecan in recurrent ovarian cancer.Compare and contrast the efficacy and safety of topotecan with other agents used for the treatment of recurrent ovarian cancer.Identify the toxicity profile of topotecan in recurrent ovarian cancer patients.

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

Ovarian cancer is the fifth leading cause of cancer death in women. Most patients with ovarian cancer respond to first-line chemotherapy, but many relapse within 18 to 22 months. The development of efficacious salvage therapies that increase overall survival while maintaining quality of life is a great challenge in the treatment of this disease. Topotecan, a novel topoisomerase I inhibitor, is currently indicated for the treatment of recurrent metastatic carcinoma of the ovary. In patients with relapsed ovarian cancer, the overall response rates on treatment with topotecan range from 19%-33% in platinum-sensitive patients, 14%-18% in platinum-resistant patients, and 5%-11% in platinum-refractory patients. The proportion of patients achieving stable disease ranges between 17% in refractory and 48% in sensitive patients. In phase III studies, topotecan was shown to be equivalent in efficacy to both paclitaxel and liposomal doxorubicin as second-line therapy in patients with relapsed ovarian cancer. Further, non-cross-resistance between topotecan and paclitaxel was demonstrated in a third-line, phase III crossover study, suggesting that topotecan may be effective in the first-line setting with paclitaxel and/or platinum. Hematologic toxicities include neutropenia, thrombocytopenia, and anemia; however, these toxicities are usually short lived, noncumulative, and manageable with dose modifications, including low-dose topotecan regimens. Nonhematologic toxicities are usually mild to moderate in severity. These data support the use of topotecan for second-line therapy and suggest that topotecan may also be effective in first-line therapy. Further studies with topotecan alone and in combination with other agents are needed to fully characterize the role and sequencing of topotecan in the salvage and first-line settings.
Update on the Treatment of Cervical and Uterine Carcinoma: Focus on Topotecan
Authors: Fiorica James V.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:Identify the need for new chemotherapeutic agents in the treatment of advanced gynecologic malignancies.Describe antitumor activity of topotecan in patients with advanced cervical cancer.Identify other gynecologic malignancies in which the use of topotecan is currently being explored.

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

Carcinomas of the uterine cervix and corpus are significant causes of morbidity and mortality among women in the U.S. and are expected to contribute 10,700 deaths in 2002. Despite the widespread use of cytologic screening and improvements in early diagnosis, mortality rates have changed little over the past 25 years, and the management of cervical and uterine cancers remains a significant unmet medical need. Currently available modalities, including radiotherapy and cisplatin-based chemotherapy, provide suboptimal control of disease, and there are no effective treatments for recurrent disease. The antitumor activity and tolerability of a number of novel agents, including topoisomerase I inhibitors, vinca alkaloids, taxanes, and gemcitabine, have been of considerable interest in treatment of these cancers. This review discusses current trends in the treatment of cervical and endometrial carcinomas, focusing on the potential role of topotecan in the treatment of non-ovarian gynecologic malignancies.
Treatment for Anthracycline-Pretreated Metastatic Breast Cancer
Authors: O'Shaughnessy Joyce , Twelves Chris , Aapro Matti
Published: August 2004

Learning Objectives

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

Recognize the chemotherapy options that provide a survival benefit for anthracycline-pretreated metastatic breast cancer. Identify some of the validated treatment options for breast cancer patients with recurrent disease following anthracycline-based therapy. Explain the rationale for specific salvage treatment regimens in patients with recurrent breast cancer following anthracyline-based therapy.

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

As a result of increasing anthracycline use earlier in the course of breast cancer, oncologists are frequently faced with the challenge of treating patients whose disease has progressed during or following anthracycline therapy or who are ineligible for further anthracycline therapy. Many of these women remain candidates for cytotoxic chemotherapy, and several treatment options exist. Until recently, the taxanes, docetaxel in particular, were widely regarded as the most effective therapy for these patients, based on a survival advantage observed with docetaxel. However, a recent phase III study demonstrated that the addition of capecitabine to docetaxel results in superior overall survival (with a 3-month improvement in median survival), superior time to disease progression, and a superior response rate, with a manageable safety profile. Capecitabine/docetaxel is the first cytotoxic combination to improve survival over standard monotherapy in patients with anthracycline-pretreated metastatic breast cancer. Moreover, the survival benefit can be attributed to the addition of capecitabine, as it was achieved despite the lower dose of docetaxel administered in the combination arm. Quality of life was maintained with capecitabine/docetaxel combination therapy, which further supports the use of this regimen in patients with anthracycline-pretreated metastatic breast cancer. Pharmacoeconomic modeling using the data from the phase III trial has shown that the capecitabine/docetaxel combination therapy is highly cost effective when compared with other cancer treatments that improve survival. This review describes several treatment options for patients with anthracycline-pretreated breast cancer, including the phase III data (efficacy, tolerability, quality of life, and pharmacoeconomics) for capecitabine plus docetaxel in this setting.
Treating Fatigue in Cancer Patients
Authors: Berger Ann
Published: August 2004

Learning Objectives

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

Explain the randomized controlled trials involving cancer patients with fatigue. Describe the different etiologies of fatigue. Describe the interventions (pharmacologic and nonpharmacologic) that are available for cancer patients with fatigue.

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

Possible causes of cancer-related fatigue include depression, pain, sleep problems, anemia, deconditioning, metabolic abnormalities, infection, dietary problems, hypoxia, and side effects of medication. Although treatments are available for each of these conditions, there are no generally accepted treatments available for the whole fatigue syndrome. There are also very few studies on the treatment of cancer-related fatigue—only 10 randomized controlled trials. Health care providers have begun to understand that, just as the treatment of pain requires attention to imbalances in mind, body, and spirit, the treatment of fatigue will require such an approach.
The Cellular Biology of Erythropoietin Receptors
Authors: Lappin Terry
Published: August 2004

Learning Objectives

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

Explain the structure and functions of erythropoietin. Distinguish the multiple activities of erythropoietin in the human body. Recognize the potential role of erythropoietin receptors in targeting tumors.

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

Long thought to act only as a hormone that was the primary regulator of red blood cell production, erythropoietin is now known to have a whole spectrum of activity. Organs such as the brain, ovary, oviduct, uterus, and testis have erythropoietin receptors. Because erythropoietin receptors exist in the paracrine and autocrine systems, as well as the hormonal system, the beneficial effects of administering human erythropoietin are likely to extend beyond its effect in raising hematocrit. It may even be possible in the future to use the receptors to target a drug to a tumor without damaging the surrounding tissue.
A Survivor's Journey: One Woman's Experience with Cancer-Related Fatigue
Authors: Gilbert Maureen
Published: August 2004

Maureen Gilbert was diagnosed at age 45 with breast cancer in Dublin, Ireland in 2000. She had a mastectomy with immediate breast reconstruction, chemotherapy, and a second prophylactic mastectomy with reconstruction. Soon after diagnosis, she began to experience fatigue that intensified to incapacitating levels with chemotherapy and stayed with her for 18 months. This experience is described in compelling terms. Fatigue was not mentioned by any of her caregivers when they spoke of symptoms and side effects. She is convinced that if the condition of fatigue had been described and validated as a symptom from the beginning, it would have helped her considerably to manage and live through it. There were some very positive outcomes from the whole experience of having cancer, but the journey would have been easier, had someone told her about fatigue.
Fatigue and Quality of Life: Lessons from the Real World
Authors: Flechtner Henning , Bottomley Andrew
Published: August 2004

Learning Objectives

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

Explain the nature and prevalence of cancer-related fatigue. Identify which instruments are currently in use for assessing fatigue. Identify patterns of recovery in cancer patients.

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

The impact of fatigue on the quality of life of oncology patients is substantial and under-recognized. Fatigue in these patients may begin with a simple decrease in physical activity, but can progress to include a wide range of negative effects that often culminate in patients feeling out of control, lonely, and isolated. In general, surviving cancer patients experience some limitations after the end of treatment but ultimately attain a reasonably good level of functioning. An examination of subpopulations and further analyses of data suggest, however, four different recovery patterns. Patients may: A) improve in their functioning, reach a plateau at approximately year 2 or 3, and then remain at relatively high levels of functioning; B) improve initially, but deteriorate again after year 2 or 3, never reaching the normal stage; C) improve, returning to normal; or D) have a very mixed pattern of high levels of fatigue that is, to date, very difficult to interpret. Disturbingly, 60% of the survivors in our population of patients with Hodgkin's disease, who were treated in recent trials of the German Hodgkin Study Group and the European Organization for Research and Treatment of Cancer Lymphoma Group, had medium to high levels of fatigue after 5 cancer-free years. Investigations are essential to determine the current status of long-term survivors in more detail and to link that status to conditions observed during the treatment of acutely ill patients.
Liposomal Anthracyclines: Adjuvant and Neoadjuvant Therapy for Breast Cancer
Authors: Campos Susana
Published: August 2004

Learning Objectives

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

Describe the role of conventional anthracyclines in the adjuvant breast cancer setting. Discuss the efficacies and tolerabilities of liposomal anthracyclines as neoadjuvant therapy in patients with locally advanced breast cancer. Explain the rationale for the future study of liposomal anthracyclines in adjuvant therapy for patients with early-stage breast cancer.

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

Conventional anthracyclines, particularly doxorubicin, have played an important role in the treatment of patients with breast cancer for many decades. Conventional doxorubicin has shown excellent antitumor activity in the metastatic, neoadjuvant, and adjuvant settings. However, its clinical utility is limited due to acute and chronic toxicities, particularly cardiotoxicity, myelosuppression, nausea and vomiting, and alopecia. Liposomal doxorubicin formulations (liposomal doxorubicin [D-99] and pegylated liposomal doxorubicin) currently under investigation for the treatment of breast cancer have demonstrated similar efficacies and favorable toxicity profiles compared with conventional doxorubicin in patients with metastatic breast cancer. These agents have also shown efficacy and tolerability in several small studies as neoadjuvant therapy in patients with locally advanced breast cancer. While there are currently no studies with liposomal doxorubicin or pegylated liposomal doxorubicin as adjuvant therapy, their demonstrated activities and tolerabilities in the metastatic and neoadjuvant settings provide the rationale for the future study of these agents in adjuvant therapy for patients with early-stage breast cancer.
Cardiac Safety of Liposomal Anthracyclines
Authors: Safra Tamar
Published: August 2004

Learning Objectives

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

Describe the cardiac toxicity profiles of conventional anthracyclines. Discuss the published data evaluating the cardiac safety of liposomal anthracyclines. Describe MUGA scan monitoring recommendations for patients treated with liposomal anthracyclines.

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

Anthracyclines have demonstrated antitumor activity in a variety of cancers; however, irreversible cardiac damage is a major dose-limiting toxicity, restricting lifetime cumulative dose. The most successful strategy to improve the cardiac safety of anthracyclines to date involves liposomal encapsulation, which alters the tissue distribution and pharmacokinetics of these agents. The cardiac safeties of liposomal daunorubicin, liposomal doxorubicin (D-99), and pegylated liposomal doxorubicin have been studied in several clinical trials. The lack of published data comparing liposomal daunorubicin with conventional daunorubicin makes it difficult to draw meaningful conclusions regarding the relative cardiac safeties of these formulations. Studies indicate that the risk of anthracycline-induced cardiotoxicity is considerably lower with liposomal doxorubicin formulations than with conventional doxorubicin. Pegylated liposomal doxorubicin has been studied most extensively and has demonstrated the most significant reductions in risk for cardiotoxicity. Compared with conventional doxorubicin, pegylated liposomal doxorubicin has shown similar efficacy with a significantly lower incidence of cardiotoxicity and significantly fewer cardiac events. Although the long-term cardiac safety of these agents is unknown, data suggest that liposomal anthracyclines, particularly pegylated liposomal doxorubicin, may offer a significant clinical benefit for patients with higher risks for anthracycline-induced cardiotoxicity.
New Insights Into Erythropoietin and Epoetin Alfa: Mechanisms of Action, Target Tissues, and Clinical Applications
Authors: Weiss Mitchell J.
Published: August 2004

Learning Objectives

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

Discuss the mechanism of action of endogenous erythropoietin and the therapeutic use of epoetin alfa to stimulate red blood cell production and improve the quality of life in patients with cancer. Explain how epoetin alfa is being investigated in alternate dosing regimens and for anemia prevention in patients with cancer. Describe how functional endogenous erythropoietin receptor signaling pathways have been demonstrated in numerous nonerythropoietic tissues, including in the central nervous system, and relate evidence for the roles of erythropoietin and epoetin alfa beyond erythropoiesis, including the therapeutic implications of these nonerythroid functions.

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

Recombinant human erythropoietin (epoetin alfa) has proven beneficial for the treatment of various anemias. The mechanism of action of endogenous erythropoietin and the therapeutic use of epoetin alfa to stimulate red blood cell production and improve the quality of life in cancer patients are reviewed here. Epoetin alfa may also attenuate the cognitive dysfunction associated with cancer therapy. Interestingly, functional endogenous erythropoietin receptor signaling pathways have been demonstrated in numerous nonerythropoietic tissues. Of particular importance, epoetin alfa confers neurotrophic and neuroprotective effects in cultured neurons and in several animal models for neurologic disease. In one clinical trial, epoetin alfa appeared to limit functional and histologic damage in patients with stroke. Therefore, in cancer patients receiving chemotherapy, the beneficial effects of epoetin alfa could be mediated not only through enhanced erythrocyte production but also via direct effects on the nervous system. Further investigation into the nonerythropoietic effects of epoetin alfa could broaden its clinical utility for patients with cancer and also provide new therapies for various neurologic disorders.