bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternate Dosing Schedules for Topotecan in the Treatment of Recurrent Ovarian Cancer
Authors: Morris Robert , Munkarah Adnan 
Published: August 2004

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract
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

Abstract

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

Abstract

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

AbstractLearning ObjectivesAfter 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.comAnthracyclines 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

Abstract

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.
Modifications to Therapy for Multiple Myeloma: Pegylated Liposomal Doxorubicin in Combination With Vincristine, Reduced-Dose Dexamethasone, and Thalidomide
Authors: Hussein Mohamad A. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Discuss the current issues surrounding the treatment of multiple myeloma. Describe how treatment modifications have improved the tolerability and efficacy of this multiple myeloma therapy. Explain recent treatment advances in this disease.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
The combination of vincristine, doxorubicin, and dexamethasone is an effective treatment for multiple myeloma that produces a more rapid response than other regimens, probably a function of the high-dose, intense steroid schedule. However, vincristine/doxorubicin/dexamethasone administration requires a 96-hour continuous infusion delivered via a central venous catheter, which necessitates hospitalization in a large number of patients and may increase the risk for infection. Moreover, the high dosages of corticosteroids required with this regimen can cause substantial toxicity. Therefore, a number of modifications to the regimen have been evaluated in an effort to improve its tolerability and efficacy. These include replacing doxorubicin with pegylated liposomal doxorubicin and using a reduced frequency of dexamethasone, and, later, the addition of thalidomide. The results of an ongoing study demonstrated that this latest regimen (including thalidomide) is associated with an improved response rate and a higher quality of response compared with previous regimens in patients with relapsed/refractory multiple myeloma. This modified regimen is well tolerated when prophylactic and supportive measures are incorporated. Although additional follow-up is required to determine the effect on survival, this modified regimen has significant potential in the management of advanced myeloma.