Antiemetic properties of megestrol acetate.
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Biomedical subjects
Publications and source records attributed to Charles Loprinzi.
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Some critics question whether research on complementary and alternative modalities for patients with cancer can be done efficiently in traditional clinical settings. This article reviews a program of complementary medicine research that has been done in a traditional clinical setting over the past 30 years. Trials using complementary therapies for both symptom management and cancer treatment done by the Mayo Clinic and the North Central Cancer Treatment Group are reviewed. Twenty-seven studies have been developed using complementary therapies, addressing such issues as mucosal and epidermal toxicity, hot flashes, lymphedema, anorexia and cachexia, insomnia, cognitive dysfunction, fatigue, and cancer treatment. Nineteen of them have been completed and have had results published in peer-reviewed clinical journals, whereas two manuscripts are in press. Two other trials have recently completed accrual, and the data are being analyzed so that manuscripts can be prepared. In addition, four clinical trials are actively accruing patients. The data presented in this article demonstrate that complementary and alternative medicine research can be done in a scientifically sound manner. Well-designed and adequately powered studies can be implemented, and large numbers of patients can be accrued. The resulting research evaluations can be published in peer-reviewed medical journals.
The National Comprehensive Cancer Network (NCCN) first published the NCCN Breast Cancer Treatment Guidelines in 1996. The Guidelines address the treatment of all stages of breast cancer across the spectrum of patient care and have been updated yearly. Adjuvant therapy for breast cancer has undergone an especially rapid evolution over the past few years. Therefore, the NCCN Breast Cancer Guidelines Panel was supplemented by additional experts to form the Adjuvant Therapy Task Force to provide a forum for an extended discussion and expanded input to the adjuvant therapy recommendations for the Breast Cancer Treatment Guidelines. Issues discussed included methods of risk-stratification for recurrence; how biologic markers such as HER2 status, quantitative estrogen receptor, or genetic markers can be incorporated as prognostic or predictive factors; and how age, menopausal status, and estrogen receptor levels impact benefits from chemotherapy and endocrine therapy. Additionally, the task force discussed the strategies for use of aromatase inhibitors in postmenopausal women and the potential incorporation of trastuzumab into adjuvant therapy of women with HER2/neu positive breast cancer. This supplement summarizes the background data and ensuing discussion from the Adjuvant Task Force meeting.
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BACKGROUND: Home total parenteral nutrition (TPN) can be lifesaving and life sustaining for some patients. However, in patients with advanced, incurable cancer, its role is controversial. A retrospective study was conducted to explore whether home TPN was associated with long-term survival (>or=1 year) in patients with metastatic disease and to identify predictive factors to enable its judicious use. METHODS: The records of all adult patients with incurable cancer were identified between 1979 and 1999. Records were reviewed in depth for survival from TPN initiation to death and for a variety of demographic and clinical factors. RESULTS: Fifty-two patients were identified. Their median age was 56 years (range, 18-83 years), and 30 (58%) were women. Malignant diagnoses included carcinoid/islet cell tumor (n=10), ovarian carcinoma (n=6), amyloidosis/multiple myeloma (n=6), colorectal carcinoma (n=5), sarcoma (n=5), pancreatic carcinoma (n=4), gastric carcinoma (n=3), lymphoma (n=2), pseudomyxoma peritonei (n=2), and other (n=9). TPN was initiated for the following reasons (indications are not mutually exclusive): alimentary tract obstruction (n=20), short bowel syndrome/malabsorption (n=16), fistula (n=11), dysmotility (n=3), nausea/emesis (n=2), anorexia (n=2), and mucositis (n=1). The median time from initiation of TPN to death was 5 months (range, 1-154 months). Sixteen patients survived >or=1 year. TPN-related complications included 18 catheter infections (1 per 2.8 catheter-years), 4 thromboses, 3 pneumothoraces, and 2 episodes of TPN-related liver disease. Tumor grade, the interval between diagnosis of metastatic disease and initiation of TPN, the presence of prominent cancer symptoms, and the administration of cancer therapy after TPN were not associated in any way with overall survival. CONCLUSIONS: The initiation of home TPN can be associated with long-term survival in very select patients with incurable cancer, and complication rates with its use appear acceptable. However, the judicious use of home TPN in this setting requires careful clinical assessment on a patient-by-patient basis.
PURPOSE: Patients with incurable cancer are faced with difficult decisions regarding whether to take chemotherapy in an attempt to preserve the quality and/or prolong the quantity of their lives. The average prolongation in survival with chemotherapy compared with best supportive care has not been well described. METHODS: We performed a literature search using PUBMED combined with expert inquiry to identify trials comparing cytotoxic chemotherapy with best supportive care. Twenty-five randomized, controlled clinical trials comparing cytotoxic chemotherapy with best supportive care were identified. Sixteen trials (64%) were in patients with non-small-cell lung cancer (NSCLC). Data were extracted and analyzed. RESULTS: Sufficient data for statistical modeling were available for NSCLC trials. The mean sample size of the NSCLC trials was 175 patients. Response rates in the treatment arms for NSCLC ranged from 7% to 42%. A relationship between response rate and survival was observed for NSCLC. The estimated relationship for NSCLC suggested that each 3.3% increase in response rate correlated, on average, with a 1-week increase in median survival, and each 2% increase in response rate correlated, on average, with a 1% increase in 1-year survival. The mean increase in 1-year survival for trials of agents with at least a 20% response rate in NSCLC was 16%. Formulas are provided to help estimate how a given response rate may effect median and 1-year survival relative to best supportive care alone for NSCLC. CONCLUSION: We found a relationship between response rate and both median and 1-year survival in NSCLC. This information may help oncologists estimate how an NSCLC chemotherapy regimen with a given response rate can, on average, impact survival relative to supportive care alone.
PURPOSE/OBJECTIVES: To present the state of knowledge and a suggested program of research related to one part of sexual functioning in female cancer survivors: libido. DATA SOURCES: Journal articles, monographs, and book chapters. DATA SYNTHESIS: Sexuality is a broadly defined term with many components. Libido is a component of sexuality and is reviewed with respect to definition, physiology, and measurement. Evidence-based interventions also are discussed. CONCLUSIONS: Most of the evidence related to enhancing libido involves testosterone, but this has not been tested in cancer survivors. Several clinical questions are yet to be answered regarding physiology as well as nonpharmacologic and pharmacologic interventions for enhancing libido. IMPLICATIONS FOR NURSING: Nurse researchers could add much to the evidence base on interventions for improving libido and, subsequently, sexual health. Implementing behavioral interventions to enhance libido would be an appropriate nursing function.
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PURPOSE: Short chain ceramides induce tumor cell apoptosis in preclinical models. Limited therapeutic options for patients with cutaneous breast cancer prompted the testing of these sphingolipids in patients with this disease. PATIENTS AND METHODS: Twenty-five patients with refractory, cutaneous breast cancer were treated twice a day with a 1% mixture of topical C2 and C6 ceramides administered in a 1:1 ratio. For the first 8 weeks, patients were not allowed to receive other antineoplastic therapy. In addition to tumor status and toxicity assessment throughout the trial, skin biopsies for evidence of apoptosis and quality of life questionnaires (FACT-BR) were completed at baseline and 1 month. RESULTS: Only one patient manifested a partial response with topical ceramides, yielding a response rate of 4% (90% confidence interval 0, 17.6%). Median cutaneous progression-free survival was 2 months. The topical ceramides were also well tolerated, with no grade 3 or 4 toxicity reported. None of the six patients who underwent serial skin biopsies showed increased tumor cell apoptosis morphologically or by the modified TUNEL assay. CONCLUSION: To our knowledge, this trial is one of the first clinical investigations of short chain ceramides. This trial's results are not promising enough to merit further study of ceramides in the manner prescribed.
This multicenter, randomized, open-label clinical trial was conducted to determine whether the combined use of nicotine patch therapy and a nicotine nasal spray would improve smoking abstinence rates compared to either treatment alone, without behavioral counseling. Data were collected at 15 regional cancer control oncology centers within the North Central Cancer Treatment Group. Of the 1384 smokers randomized to the study, 20% were abstinent from smoking at 6 weeks and 8% were abstinent at 6 months. At 6 weeks, the 7-day point prevalence smoking abstinence rate for the patch alone (21.1%) was superior to the spray (13.6%) but was significantly lower than the rate for combination therapy (27.1%). At 6 months, the 7-day point prevalence abstinence rates were not significantly different among the three groups. Combination nicotine nasal spray and nicotine patches were delivered safely in a nonspecialized outpatient clinical setting and enhanced short-term smoking abstinence rates, but these rates were not sustained at 6 months.
To evaluate the efficacy of a long-acting preparation of medroxyprogesterone acetate for hot flash management, 3 men receiving androgen ablation therapy for prostate cancer and 15 women with a history of breast cancer were treated as part of clinical practice with three biweekly intramuscular injections of 500 mg depomedroxyprogesterone. A review of hot flash diaries and patient charts were completed to evaluate the effectiveness and tolerability of these injections for managing hot flashes. Treatment was associated with an approximate 90% decrease in hot flashes (95% CI 82-97%). Daily hot flash frequency decreased from a mean of 10.9 on the first day of treatment (95% CI 8.0-13.8 hot flashes per day) to a mean of 1.1 hot flashes 6 weeks later (95% CI 0.5-1.8 hot flashes) and to a mean of 0.7 hot flashes 12 weeks following therapy initiation (95% CI 0.1-1.2). Improvement in the hot flashes remained for months after discontinuing the injections in many patients. Reported side effects were minimal. This experience suggests that treatment with depomedroxyprogesterone may be an effective and well-tolerated option for the treatment of hot flashes.
Chemotherapy-induced cognitive dysfunction in women with breast cancer has become an increasingly important clinical issue. To date, little is known about its incidence, exact characteristics, and exact pathophysiology. Likewise, no treatments have been shown to prevent or decrease cognitive changes thought to result from chemotherapy. However, ongoing scientific research might help us understand the mechanisms that will help patients maintain maximal cognitive function. Changes in cognition due to chemotherapy might result from indirect chemical toxicity and oxidative damage, direct injury to neurons, inflammation, or a type of autoimmune response. Based on these potential causes, and based on interventions that have been tested in dementia and Alzheimer's disease, there are a number of potential, novel interventions that could be tested in clinical trials as treatments for chemotherapy-induced cognitive dysfunction. Possible anecdotal strategies to consider include hormonal interventions, antioxidants, monoamine oxidase inhibitors, growth factors, dopamine agonists, cholinesterase inhibitors, antiinflammatory agents, and behavioral interventions
Menopause can be experienced prematurely by women with cancer and, as such, is often accompanied by symptoms that are becoming salient management issues. It is common practice to avoid estrogen replacement therapy in women with estrogen-sensitive tumors. Therefore, the effective management of vasomotor symptoms, urogenital problems, and the prevention of osteoporosis and cardiac disease requires knowledge of nonhormonal interventions. This article discusses the changes women experience during menopause and the symptoms to which these changes can contribute. Pharmacologic options without estrogen, as well as nonpharmacologic interventions, are presented for the treatment of hot flashes, vaginal dryness, and urinary incontinence, and the maintenance of skin, bone, and heart health. The issue of cognitive dysfunction is also addressed. For most of the problems associated with menopause, viable, effective options are available for cancer survivors.
OBJECTIVE: Hot flashes are a significant problem in women going through the menopausal transition that can substantially affect quality of life. The world of estrogen therapy has been thrown into turmoil with the recent results of the Women's Health Initiative trial report. Pursuant to a growing interest in the use of alternative therapies to alleviate menopausal symptoms and a few pilot trials that suggested that acupuncture could modestly alleviate hot flashes, a prospective, randomized, single-blind, sham-controlled clinical trial was conducted in women experiencing hot flashes. DESIGN: Participants, after being randomized to medical versus sham acupuncture, received biweekly treatments for 5 weeks after a baseline assessment week. They were then followed for an additional 7 weeks. Participants completed daily hot flash questionnaires, which formed the basis for analysis. RESULTS: A total of 103 participants were randomized to medical or sham acupuncture. At week 6 the percentage of residual hot flashes was 60% in the medical acupuncture group and 62% in the sham acupuncture group. At week 12, the percentage of residual hot flashes was 73% in the medical acupuncture group and 55% in the sham acupuncture group. Participants reported no adverse effects related to the treatments. CONCLUSIONS: The results of this study suggest that the used medical acupuncture was not any more effective for reducing hot flashes than was the chosen sham acupuncture.
PURPOSE/OBJECTIVES: To evaluate the intermediate term efficacy and toxicity of the use of venlafaxine for the control of hot flashes. DESIGN: An open-label continuation phase study following a double-blind, randomized, placebo-controlled clinical trial that tested three doses of venlafaxine for the control of hot flashes. SETTING: North Central Cancer Treatment Group institutions. SAMPLE: 102 postmenopausal women. METHODS: Women could titrate venlafaxine to optimum efficacy while recording daily hot flash counts and weekly toxicity information. MAIN RESEARCH VARIABLES: Hot flash frequency, hot flash score. FINDINGS: The reduction in hot flashes previously reported in the randomized study phase was maintained during the open-label study. Toxicity did not appear to increase over time. CONCLUSIONS: The data from this study provides evidence that venlafaxine has intermediate term efficacy and good tolerability as a treatment for hot flashes. IMPLICATIONS FOR NURSING PRACTICE: Nurses can inform symptomatic women that an effective nonhormonal alternative exists to control their hot flashes.