Megestrol acetate-induced adrenal suppression.
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Biomedical subjects
Publications and source records attributed to C L Loprinzi.
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OBJECTIVE: To characterize a clinical syndrome that occurs in some women who have undergone breast or axillary lymph node biopsy or partial mastectomy. MATERIAL AND METHODS: Six case reports are presented, the clinical and histopathologic findings are described, and the implications for recognition of this entity are discussed. RESULTS: Patients who had undergone partial mastectomy, breast biopsy, or axillary lymph node excision shortly thereafter had clinical signs (most notably, erythema and edema) suggestive of infectious mastitis or inflammatory breast cancer. Representative histologic sections of involved skin revealed dilated dermal vessels without specific evidence of infection or cancer. Although antibiotic therapy was generally ineffective, the clinical findings resolved with time (from 2 months to 1 year). This condition should be considered in the differential diagnosis when this circumscribed patient population has such intervention-related symptoms. CONCLUSION: This clinical syndrome may mimic an infectious or neoplastic process, but we hypothesize that it is due to interruption of lymphatic vessels. Appropriate recognition may alter the use of antibiotic therapy or surgical intervention.
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This intergroup trial was developed to determine the toxicity of relatively low doses of difluoromethylornithine (DFMO) administered to humans for 1 year. The goal was to find an appropriate DFMO dose for use in human chemoprevention trials. Patients with resected superficial bladder cancers were studied. Following stratification, they were randomized to daily DFMO doses of 0.125, 0.25, 0.5, or 1.0 g/day for a planned period of 1 year. Patients were followed closely for evidence of drug toxicity. Seventy-six patients were evenly randomized (19 per group) to receive each dose of DFMO. Forty-nine patients received DFMO for more than 200 days while 35 received the drug for > or = 350 days. No substantial drug-related toxicity was observed at any dose. DFMO doses of > or = 1 g/day for periods up to 1 year appear to be without significant toxicity in most patients. This dose range may be appropriate for use in future human cancer chemoprevention trials.
OBJECTIVE: To determine the effectiveness of follow-up tests for signaling recurrences in patients with intermediate- and high-risk malignant melanomas treated with curative intention. DESIGN: Retrospective analysis of prospectively collected data. SETTING: North Central Cancer Treatment Group. PATIENTS: A total of 261 patients with resected local (> or = 1.69 mm) and regional nodal malignant melanomas who were enrolled in a single prospective adjuvant trial were studied. All patients were scheduled to be followed up monthly for 2 months, then every 2 months for the first year, every 4 months the second year, every 6 months the next 3 years, and annually thereafter, with each visit consisting of a history, physical examination, complete blood cell count, blood chemistry panel, and a chest x-ray. RESULTS: Of the 145 evaluable patients who developed recurrent melanomas, 99 patients (68%) developed symptoms that signaled the diagnosis of recurrent disease. Physical examination of asymptomatic patients led to the diagnosis of recurrent disease in 37 patients (26%). The other nine patients (6%) with recurrent disease had abnormal chest x-rays. Laboratory results were never a sole indicator of recurrent disease. CONCLUSION: The majority of recurrences following resection of primary melanomas are discovered by history and/or physical examination despite the frequent use of other follow-up tests. The present data indicate that routine blood analyses and chest x-rays have limited value in the postoperative follow-up of patients with resected intermediate- and high-risk melanomas.
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Cancer anorexia/cachexia is a common clinical problem that substantially impacts upon the quality of life and survival of affected patients. Extensive investigations have not supported the use of either enteral or paternal hyperalimentation for such patients. Despite positive pilot trial reports, large randomized studies have been unable to demonstrate a clinically defensible role for either pentoxifylline, cyproheptadine, or hydrazine sulfate for patients with anorexia. Multiple placebo-controlled, randomized, double-blind, clinical trials have demonstrated that corticosteroids do have appetite-enhancing properties in patients suffering from cancer anorexia/cachexia, but none of these studies has demonstrated weight gain. In comparison, multiple studies have demonstrated that the progestational agent, megestrol acetate, has both appetite-enhancing and weight-promoting properties.
Sedation may be a dose-limiting side-effect of opioid therapy in some cancer patients. This study was designed to evaluate further the use of the psychostimulant, methylphenidate, an agent that has been reported to counter-act opioid-induced sedation, in patients with cancer-related pain. Patients receiving a stable dose of an opioid for cancer-related pain were recruited for this randomized, double-blind, crossover clinical trial. In addition to their regular dose of narcotics, they received 5 days of methylphenidate followed by 5 days of placebo, or vice versa. Our data did not definitively demonstrate any statistically significant benefit for methylphenidate, but did suggest that this drug could mildly decrease narcotic-induced drowsiness and could increase night-time sleep. These data, in conjunction with other published data, suggest that methylphenidate can counteract narcotic-induced daytime sedation to a limited degree.
PURPOSE: Based on evidence that suggests pentoxifylline can inhibit tumor necrosis factor, we set out to evaluate the activity and toxicity of this drug in patients with cancer-associated anorexia and/or cachexia. PATIENTS AND METHODS: Seventy patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 with cancer anorexia and/or cachexia (defined by a weight loss of > or = 5 lb in the preceding 2 months or a caloric intake < 20 kcal/kg/d) were stratified and then randomly assigned to receive pentoxifylline or identical-appearing placebo tablets in a double-blind fashion. Patients' weights were monitored and patient questionnaires were used to assess appetite, toxicity, and perception of benefit. RESULTS: Pentoxifylline failed to improve the appetites of study patients. Pentoxifylline did not appear to cause any toxicity. CONCLUSION: This study failed to demonstrate any benefit of pentoxifylline at this dose and schedule as therapy for cancer anorexia and/or cachexia.
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Cytotoxic chemotherapy and radiation therapy damage normal body tissues, resulting in stomatitis, conjunctivitis, esophagitis, proctitis, and dermatitis. Pursuant to this, the North Central Cancer Treatment Group has developed a series of clinical trials designed to study antidotes for these pathologic processes. These trials have demonstrated clinically helpful therapies (eg, oral cryotherapy for decreasing mucositis induced by 5-fluorouracil) and also have demonstrated lack of benefit for other proposed treatments. Results from several ongoing clinical trials should become available in the near future.
BACKGROUND: Doxorubicin generally is considered to be the most effective single chemotherapeutic agent for the treatment of breast cancer. The major cumulative dose-limiting toxicity is cardiac toxicity, which may be related to the formation of free radicals with subsequent lipid peroxidation, leading to membrane damage. The anthrapyrazoles, of which piroxantrone is a member, were synthesized in an attempt to eliminate this toxicity. METHODS: A Phase II clinical trial was conducted in 30 women with metastatic breast cancer in whom piroxantrone was administered at a dose of 160 mg/m2 by 1-hour infusion. The planned cycle length for retreatment was 3 weeks. Measurable metastatic disease and failure on one prior chemotherapy regimen, but no prior anthracycline exposure, were required for response evaluation. RESULTS: Twenty-nine patients were evaluable for response, and 6 (21% and 95% confidence intervals: 10-43%) achieved an objective response (1 complete, 5 partial responses), with a median response duration of 244 days. The median time-to-disease progression for all patients was 124 days. Eight patients received cumulative doses of piroxantrone approaching or exceeding 1000 mg/m2, and all had reductions in the resting left ventricular ejection fraction (LVEF). The estimated median decrease in LVEF at 1000 mg/m2 was 16%, with a range of 10-28%. Clinical findings of congestive heart failure developed in two patients. CONCLUSIONS: Piroxantrone had definite antitumor activity in women who had metastatic breast cancer and failure on prior chemotherapy that did not include an anthracycline. The 95% confidence interval for response probability was broad, but the level of activity observed was relatively low. The clear association with cardiac toxicity combined with the relatively low efficacy led to the conclusion that piroxantrone cannot be recommended for further development as therapy for women with breast cancer. Further study of other anthrapyrazoles is necessary to determine if the promise of this new class of agents can be fulfilled.
BACKGROUND: Vasomotor hot flashes are a common symptom in women during menopause and in men who have undergone androgen-deprivation therapy for prostate cancer. Although treatment with estrogens in women and androgens in men can attenuate these symptoms, these hormones may be contraindicated in women with breast cancer and in men with prostate cancer. Pilot trials have suggested that the progestational agent megestrol acetate can ameliorate hot flashes in both groups of patients. METHODS: The patients included 97 women with a history of breast cancer and 66 men with prostate cancer who had undergone androgen-deprivation therapy. All patients had experienced bothersome hot flashes (median number per day at base line, 6.1 for the women and 8.4 for the men). After a one-week pretreatment observation period, the patients received megestrol acetate (20 mg twice daily) for four weeks, followed by placebo for four weeks, or vice versa in a double-blind manner as determined by pretreatment randomization. The patients documented the frequency and severity of hot flashes in daily symptom diaries. RESULTS: After four weeks, hot flashes were reduced by 21 percent in the group receiving placebo first and by 85 percent in the group receiving megestrol acetate first (P < 0.001). An intention-to-treat analysis of data for all eligible treated patients showed that 74 percent of the megestrol acetate group, as compared with 20 percent of the placebo group, had a decrease of 50 percent or more in the frequency of hot flashes during the first four weeks (P < 0.001). The degree of efficacy was similar in men and women. The only side effect was withdrawal menstrual bleeding in women, generally occurring one to two weeks after the megestrol acetate had been discontinued. CONCLUSIONS: Low-dose megestrol acetate is well tolerated and can substantially decrease the frequency of hot flashes in women and men.
BACKGROUND: This clinical trial was developed to determine whether ocular ice pack therapy would decrease 5-fluorouracil (5-FU)-induced ocular toxicity. METHODS: Sixty-two patients who suffered from 5-FU-induced ocular toxicity, and were scheduled to receive another cycle of the chemotherapy that caused the ocular toxicity, were entered in this clinical trial. A randomized, crossover design was used, with patients documenting their ocular toxicity by the use of daily diaries. RESULTS: The results from the first cycle of treatment suggested that ocular ice pack therapy decreased 5-FU-induced ocular toxicity (P = 0.056). The 38 evaluable patients in the crossover analyses demonstrated decreased ocular toxicity with ocular ice pack therapy (p = .001). The ocular ice pack therapy was well tolerated by most of the study participants. CONCLUSION: Ocular ice pack therapy appears to lessen 5-FU-induced ocular toxicity to a clinically moderate degree. Better methods for decreasing 5-FU-induced ocular toxicity are necessary.
Procedure-related pain is a significant problem for many children receiving cytotoxic chemotherapy. In an effort to lessen this toxicity, we studied the efficacy and safety of administering topical local anesthesia using EMLA cream in 47 evaluable children with cancer undergoing implanted central venous port injections. Children (< 21 years old) scheduled to undergo repeated venous access procedures were selected for study. A placebo-controlled, randomized, double-blind, crossover study design was utilized. Statistically significant decreases in pain intensity scores (P < 0.002) were recorded by both children and investigators during the use of EMLA cream as compared with placebo. There was a good correlation between pain scores recorded by both patients and health care providers using both visual analog scales and categorized pain measurement tools. The topical application of EMLA cream 5% provides highly effective superficial anesthesia, and promises to be extremely useful for pain relief during percutaneous access procedures in cancer patients.
To determine the efficacy of transdermal clonidine for alleviating post-orchiectomy hot flashes, a randomized, double-blind, crossover clinical trial was designed including 70 men with a history of prostate cancer who had undergone a medical or surgical orchiectomy and were suffering from hot flashes. The results of this study demonstrated that clonidine did not significantly decrease hot flash frequency or severity. Future research is necessary to find effective means of alleviating hot flashes in post-orchiectomy patients.
OBJECTIVE: To summarize the important principles of opioid analgesia for cancer-related pain. DESIGN: We reviewed our personal experience and reports in the literature to characterize commonly prescribed high-potency opioids and their relative efficacy. MATERIAL AND METHODS: The pharmacologic features of various opioids, selection of appropriate agents, titration of doses, routes of administration, conversions between drugs, and management of side effects are discussed. RESULTS: In general, the oral route is preferred because of ease of administration and good oral bioavailability of most opioids. In addition to the scheduled dosage of an opioid, extra "rescue" doses (5 to 10% of the total daily opioid dosage) should be available to the patient for breakthrough pain. Morphine is the prototype strong opioid against which other drugs are compared. Common adverse effects of opioids are sedation, nausea, constipation, respiratory depression, and myoclonus. Although no "standard" dose of opioid exists, the goals are to achieve adequate control of pain and to avoid major, unmanageable toxic effects. CONCLUSION: Pain is commonly associated with all stages of malignant disease. Despite its widespread occurrence, cancer pain is often inadequately managed because of poor assessment of pain and physicians' misconceptions about use of opioids. The cause of the pain should be carefully sought because it may yield important information about the underlying malignant disease. In most patients with moderate to severe cancer-related pain, oral administration of the appropriate opioid will achieve effective analgesia.