Phase III, Randomized, Double-Blind, Placebo-Controlled Evaluation of Pregabalin for Alleviating Hot Flashes, N07C1

PURPOSE: Hot flashes are a common problem for which effective and safe treatments are needed. The current trial was conducted on the basis of preliminary promising data that pregabalin decreased hot flashes. PATIENTS AND METHODS: A double-blind, placebo-controlled, randomized trial design was used to compare pregabalin at target doses of 75 mg twice daily and 150 mg twice daily with a placebo. Hot flash frequencies and scores (frequency times mean severity) were recorded daily during a baseline week and for six treatment weeks. The primary end point for this study was the change-from-baseline hot flash score during treatment week 6 between the 150 mg twice daily target pregabalin treatment and placebo. Nonparametric Wilcoxon rank sum tests, two-sample t tests, and chi(2) tests were used to compare the primary and secondary hot flash efficacy end points between pregabalin treatments and placebo. RESULTS: Hot flash score changes available for 163 patients during the sixth treatment week compared with a baseline week decreased by 50%, 65%, and 71% in the placebo, and target 75 mg twice daily and 150 mg twice daily pregabalin arms, respectively (P = .009 and P = .007, comparing respective pregabalin arms to the placebo arm). While some toxicities were significantly more common in the pregabalin arms, being more evident with the higher dose, pregabalin was generally well tolerated by most patients. CONCLUSION: Pregabalin decreases hot flashes and is reasonably well tolerated. A target dose of 75 mg twice daily is recommended. Its effects appear to be roughly comparable to what has been reported with gabapentin and with some newer antidepressant

Association of physical activity on memory interference: Boston Puerto Rican Health Study

Background: The objective of this study was to evaluate the association between habitual physical activity engagement on memory interference. The present analysis used cross-sectional data from the Boston Puerto Rican Health Study (n=1,241; mean age= 57.2; 72.1% female). Methods: Physical activity was evaluated via self-report. Memory interference was evaluated using a word-list paradigm. The memory task included learning a list of 16 words (List A; 5 trials), followed by a distractor list (List B), and then an immediate recall of List A. Proactive interference occurs when preceding stimuli (e.g., Trial 1 and Trial 5 of List A) interferes with performance on a subsequent stimuli (List B). Retroactive interference occurs when subsequent stimuli (List B) interferes with the recall of previously encoded stimuli (Trial 5). Results: For proactive interference, there was no association between physical activity and the difference between performance on List B and Trial 1 of List A (β=0.00001; P= 0.96). Similarly, for retroactive interference, there was no association between physical activity and the difference between the short delay recall and Trial 5 of List A (β=0.0002; P= 0.50). Conclusion: The present study did not observe an association between habitual physical activity on attenuating memory interference

A Pilot Evaluation of Alternating Preoperative Chemotherapy in the Management of Patiens with Locoregionally Advanced Breast Carcinoma

BACKGROUND: This prospective trial was conducted to evaluate the outcome of patients treated with preoperative and post operative chemotherapy, mastectomy, and irradiation for locoregionally advanced breast carcinoma. METHODS: Between June 1986 and September 1990, 71 patients received 2 cycles of doxorubicin that alternated with 2 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil prior to mastectomy; irradiation was administered when the tumor was not amenable to surgical resection. Additional chemotherapy and tamoxifen, in hormone receptor-positive tumors, was used after mastectomy. Post-operative irradiation was given on a selective basis for patients at high risk for locoregional disease recurrence. RESULTS: Although 5 patients (7%) had disease progression, clinical partial or complete tumor response to preoperative chemotherapy was noted in 46 patients (65%). Sixty-eight patients (96%) underwent mastectomy. With a median follow-up of 52 months, the relapse-free and overall survival rates at 5 years were 42% and 57% respectively. Locoregional tumor recurrence occurred in 14 patients (20%), and 28 patients (39%) developed metastatic disease. Menopausal status, clinical presentation (noninflammatory vs. inflammatory), and American Joint Committee on Cancer clinical stage were independent covariates associated with patient outcome. CONCLUSIONS: Preoperative alternating chemotherapy, with the selective use of irradiation, resulted in significant locoregional disease regression and the successful integration of mastectomy into the therapeutic strategy. Locoregional tumor control and relapse-free and overall survival estimates for the approach described herein compared favorably with other comtemporary reports for this condition

Effects of acute exercise intensity on source episodic memory and metamemory accuracy

Prior research suggests that behavioural (e.g., exercise) and psychological factors (e.g., metamemory; monitoring and control of one’s memory processes) may influence memory function. However, there is conflicting results on the optimal intensity of acute exercise to enhance memory and whether acute exercise can also enhance metamemory. Furthermore, very limited research has evaluated whether acute exercise can influence source episodic memory. The objective of this study was to evaluate whether there is an intensity-specific effect of acute exercise on source episodic memory and metamemory accuracy. Thirty young adults participated in a three-condition (control/moderate/vigorousintensity exercise), within-subject counterbalanced experimental study. After each intervention, participants completed source episodic memory and metamemory tasks. Results demonstrated that acute exercise, relative to control, was effective in enhancing source episodic memory, but not metamemory accuracy. Vigorous-intensity acute exercise was the most optimal intensity to enhance source episodic memory. Overall, our findings suggest that there is an intensityspecific effect of acute exercise on source episodic memory. Furthermore, when exercise-related improvements in memory occur, young adults may be unaware of these memory benefits from exercise

Association of physical activity on memory interference: Boston Puerto Rican Health Study

Background: The objective of this study was to evaluate the association between habitual physical activity engagement on memory interference. The present analysis used cross-sectional data from the Boston Puerto Rican Health Study (n=1,241; mean age= 57.2; 72.1% female). Methods: Physical activity was evaluated via self-report. Memory interference was evaluated using a word-list paradigm. The memory task included learning a list of 16 words (List A; 5 trials), followed by a distractor list (List B), and then an immediate recall of List A. Proactive interference occurs when preceding stimuli (e.g., Trial 1 and Trial 5 of List A) interferes with performance on a subsequent stimuli (List B). Retroactive interference occurs when subsequent stimuli (List B) interferes with the recall of previously encoded stimuli (Trial 5). Results: For proactive interference, there was no association between physical activity and the difference between performance on List B and Trial 1 of List A (β=0.00001; P=0.96). Similarly, for retroactive interference, there was no association between physical activity and the difference between the short delay recall and Trial 5 of List A (β=0.0002; P=0.50). Conclusion: The present study did not observe an association between habitual physical activity on attenuating memory interference

Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individual's specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting

BACKGROUND We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide–doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P = 0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P = 0.002), and the overall 120-hour period (37% vs. 22%, P = 0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P = 0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.

Dexamethasone to prevent everolimus-induced stomatitis (Alliance MIST trial: A221701)

mTOR inhibitors such as everolimus may cause oral stomatitis, often a dose-limiting toxicity. Prior clinical research has suggested that a dexamethasone mouth rinse might help prevent and/or treat this. Alliance A221701 was a randomized phase III trial of patients initiating 10 mg daily oral everolimus that compared dexamethasone mouthwash taken preventively (initial dexamethasone group) versus therapeutically (initial placebo group) to assess two coprimary endpoints: the incidence of mTOR inhibitor-associated stomatitis (mIAS), and the area under the curve (AUC) of mIAS-associated pain over an 8-week treatment period. A Fisher\u27s exact test was used to compare the incidences while a Wilcoxon rank-sum test was used to compare the AUCs. In addition, we performed an exploratory analysis of the association of everolimus trough concentrations and toxicity using a Mann-Whitney U test. Due to slow accrual, this study closed after 39 patients were randomized (19 to upfront placebo and 20 to upfront dexamethasone). There were no significant differences between groups seen in either of the coprimary endpoints; furthermore, we found no association between whole blood everolimus trough concentrations and toxicity. Although limited by poor enrollment, the results of this study do not suggest that prophylactic dexamethasone mouthwash is superior to therapeutic dexamethasone mouthwash (initiated at the first sign of mouth pain) for reducing the incidence or severity of mIAS from everolimus

Switching to letrozole or exemestane improves hot flushes, mood and quality of life in tamoxifen intolerant women

We report an open-label, prospective, crossover study involving 184 post-menopausal women experiencing hot flushes on adjuvant tamoxifen (T). Six weeks after switching to an AI, the primary end point, hot flush score, improved by 47.3% (P<0.001) compared to those reported on T. The mean mood rating scale (MRS) score improved by 9.7% (P=0.01). The total mean combined FACT (b+es) score improved from 134.2 (95% CI ±2.96) to 143.5 (95% CI ±2.96 <0.001), and the endocrine subscale improved by 9.8% from 51.73 (95% CI ±1.38) to 57.34 (CI ±1.38, P<0.001). At 6 weeks, significantly more women chose to remain on an AI: 133 (72%), vs 40 (22%) (P<0.001) preferring T. At 3 months, 107 (58%) preferred to remain on an AI, 55(30%) on T, and 22 (12%) withdrew. The overall arthralgia rate at 3 months was 47% on AI and 30% on T (P=0.001). In all 182 (99%) women reported appreciating the opportunity to experience both drugs. These data suggest that if patients suffering significant adverse effects on T are given the opportunity to try an AI, this empowers them to prioritise relative side-effects, improving wellbeing in a significant proportion. These data also highlight the need for hospital follow-up in this intolerant cohort