Bradley J. Christensen

Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial

BACKGROUND Hot flashes can be troublesome, especially when hormonal therapy is contraindicated. Preliminary data have suggested that newer antidepressants, such as venlafaxine, can diminish hot flashes. We undertook a double-blind, placebo-controlled, randomised trial to assess the efficacy of venlafaxine in women with a history of breast cancer or reluctance to take hormonal treatment because of fear of breast cancer. METHODS Participants were assigned placebo (n=56) or venlafaxine 37.5 mg daily (n=56), 75 mg daily (n=55), or 150 mg daily (n=54). After a baseline assessment week, patients took the study medication for 4 weeks. All venlafaxine treatment started at 37.5 mg daily and gradually increased in the 75 mg and 150 mg groups. Patients completed daily hot-flash questionnaire diaries. The primary endpoint was average daily hot-flash activity (number of flashes and a score combining number and severity). Analyses were based on the women who provided data throughout the baseline and study weeks. FINDINGS 191 patients had evaluable data for the whole study period (50 placebo, 49 venlafaxine 37.5 mg, 43 venlafaxine 75 mg, 49 venlafaxine 150 mg). After week 4 of treatment, median hot flash scores were reduced from baseline by 27% (95% CI 11-34), 37% (26-54), 61% (50-68), and 61% (48-75) in the four groups. Frequencies of some side-effects (mouth dryness, decreased appetite, nausea, and constipation) were significantly higher in the venlafaxine 75 mg and 150 mg groups than in the placebo group. INTERPRETATION Venlafaxine is an effective non-hormonal treatment for hot flashes, though the efficacy must be balanced against the drugs side-effects. Confirmation of the results of this 4-week study awaits the completion of three ongoing randomised studies to assess the effects of other related antidepressants for the treatment of hot flashes.

Randomized Comparison of Megestrol Acetate Versus Dexamethasone Versus Fluoxymesterone for the Treatment of Cancer Anorexia/Cachexia

PURPOSE Previous double-blind, placebo-controlled, randomized clinical trials have demonstrated that both corticosteroids and progestational agents do partially alleviate cancer anorexia/cachexia. Pilot information suggested that an anabolic corticosteroid might also improve appetite in patients with cancer anorexia/cachexia. The current trial was developed to compare and contrast a progestational agent, a corticosteroid, and an anabolic corticosteroid for the treatment of cancer anorexia/cachexia. PATIENTS AND METHODS Patients suffering from cancer anorexia/cachexia were randomized to receive either dexamethasone 0. 75 mg qid, megestrol acetate 800 mg orally every day, or fluoxymesterone 10 mg orally bid. Patients were observed at monthly intervals to evaluate weight changes and drug toxicity. Patients also completed questionnaires at baseline and at monthly intervals to evaluate appetite and drug toxicities. RESULTS Fluoxymesterone resulted in significantly less appetite enhancement and did not have a favorable toxicity profile. Megestrol acetate and dexamethasone caused a similar degree of appetite enhancement and similar changes in nonfluid weight status, with nonsignificant trends favoring megestrol acetate for both of these parameters. Dexamethasone was observed to have more corticosteroid-type toxicity and a higher rate of drug discontinuation because of toxicity and/or patient refusal than megestrol acetate (36% v 25%; P =.03). Megestrol acetate had a higher rate of deep venous thrombosis than dexamethasone (5% v 1%; P =.06). CONCLUSION Whereas fluoxymesterone clearly seems to be an inferior choice for treating cancer anorexia/cachexia, megestrol acetate and dexamethasone have similar appetite stimulating efficacy but differing toxicity profiles.

Pilot Evaluation of Gabapentin for Treating Hot Flashes

OBJECTIVE To obtain pilot prospective data regarding the efficacy and tolerability of gabapentin for alleviating hot flashes. PATIENTS AND METHODS This prospective single-arm clinical trial was conducted between July 26, 2001, and November 30, 2001. Patients underwent a baseline week and then 4 weeks of gabapentin treatment, with increasing doses during the first 3 weeks, from 300 to 600 to 900 mg/d. Data were obtained primarily from patient-completed questionnaires. RESULTS Data from 20 evaluable women (of 24 entered in the trial) were available. Four patients discontinued use of gabapentin for perceived drug-related untoward symptoms, primarily related to light-headedness and dizziness. The 16 patients who completed this clinical trial had a mean reduction in hot flash frequency, in the fourth treatment week compared to the baseline week, of 66%. Their corresponding hot flash score (frequency times average severity) reduction was 70%. Additionally, patients who completed the 4 treatment weeks had a strong tendency to report an improvement in several other symptoms. CONCLUSION Although a double-blind placebo-controlled clinical trial should be conducted to better elucidate the efficacy and toxicity of gabapentin in patients with hot flashes, the available data suggest that gabapentin is a reasonable treatment to consider in patients with hot flashes if they do not wish to use hormonal therapy.

Pilot Evaluation of Paroxetine for Treating Hot Flashes in Men

OBJECTIVE To provide prospective information on the potential utility of paroxetine for treating hot flashes In men receiving androgen ablation therapy for prostate cancer. PATIENTS AND METHODS Men with symptomatic androgen ablation therapy-related hot flashes were entered into this clinical trial between August 2001 and October 2003. After a baseline week of documentation of the frequency of hot flashes, patients were assigned to receive paroxetine; the initial dosage was 12.5 mg/d, and it was increased to 37.5 mg/d over the ensuing 4 weeks. RESULTS Of the 24 patients in whom medication was initiated, 18 completed the 5-week study. In these patients, the median frequency of hot flashes decreased from 6.2 per day during the baseline week to 2.5 per day during the last study week. Hot flash scores (frequency x mean severity) during the same period decreased from 10.6 per day to 3.0 per day. Overall, paroxetine was well tolerated by most patients. CONCLUSION The results from this trial suggest that paroxetine Is an effective agent for diminishing hot flashes in men receiving androgen ablation therapy.

History of the Development of Antiemetic Guidelines at Mayo Clinic Rochester

This article describes the historic experience of the development of antiemetic guidelines for patients taking chemotherapy drugs at Mayo Clinic Rochester. The initial guidelines for the use of serotonin (5-hydroxytryptamine3) receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting were developed in early 1995 and implemented in September 1995. In February 1997, the guidelines were reviewed and modified. In the spring of 1998, major changes were made based on new data from the literature and discussions with antiemetic authorities in the United States. These guidelines were implemented in July 1998. The guidelines were again reviewed and modified in December 1998. In addition, we compared costs associated with the 1997 guidelines and the December 1998 guidelines. The developed guidelines, utilizing clinically available agents, seem to provide high-quality patient care at a reasonable cost.

Pilot evaluation of paroxetine for alleviation of hot flashes in men

8016 Background: Effective and nontoxic nonhormonal means of alleviating hot flashes are desirable for men with androgen-ablation related hot flashes. Based on positive pilot information suggesting that relatively low doses of paroxetine were able to alleviate hot flashes in women (with subsequent placebo-controlled data in women confirming the efficacy of this agent in women), we developed a phase II trial of paroxetine in men with bothersome hot flashes related to androgen ablation therapy. METHODS Participants kept a daily hot flash diary during a baseline week and then during four treatment weeks while they received paroxetine SR in the following manner: 12.5 mg/d for one week, then 25 mg/d for one week, then 37.5 mg/d for one week, and then either 25 mg/d or 37.5 mg/d for the last week (patient preference). A total of 26 patients were entered on this study between 8/6/2001 and 10/22/2003. Two patients canceled before receiving treatment, 2 patients did not returned any questionnaires, and 4 patients did not complete all 4 weeks of their diaries. RESULTS Hot flash information on the 18 evaluable study patients are provided in the table, illustrating mean hot flash score (daily frequency times average severity) data compared to the baseline week (where patients had a mean of 14.8 hot flashes per day). For comparison, similarly obtained data from a previous pilot trial, examining venlafaxine in men with hot flashes, is also illustrated. The paroxetine was tolerated well overall, with most patients reporting an improvement, during the weeks they were receiving paroxetine compared to the baseline week, in most of the potential side effects that we followed. CONCLUSIONS These preliminary data support paroxetine as a potentially effective nonhormonal agent for managing hot flashes in men. [Figure: see text] [Table: see text].