Joseph A. Roscoe

Differential Effects of Paroxetine on Fatigue and Depression: A Randomized, Double-Blind Trial From the University of Rochester Cancer Center Community Clinical Oncology Program

PURPOSE Fatigue and depression typically occur together in cancer patients, suggesting a common etiology, perhaps based on serotonin. This randomized clinical trial tested whether paroxetine, a selective serotonin reuptake inhibitor antidepressant known to modulate brain serotonin, would reduce fatigue in cancer patients and whether any reduction was related to depression. PATIENTS AND METHODS Cancer patients undergoing chemotherapy for the first time were assessed for fatigue. Of 704 patients who reported fatigue at their second chemotherapy cycle, 549 patients were randomly assigned to receive either 20 mg of oral paroxetine hydrochloride daily or placebo for 8 weeks. The assessments of fatigue and depression were performed at cycles 3 and 4 of chemotherapy. RESULTS A total of 244 patients treated with paroxetine and 235 patients treated with placebo provided assessable data. No difference was detected in fatigue between patient groups. At the end of the study, there was a difference between groups in the mean level of depression (Center for Epidemiologic Studies Depression scores, 12.0 v 14.8, respectively; P <.01). CONCLUSION Paroxetine had no influence on fatigue in patients receiving chemotherapy. A possible explanation is that cancer-related fatigue does not involve a reduction in brain 5-HT levels.

Prevalence, Demographics, and Psychological Associations of Sleep Disruption in Patients With Cancer: University of Rochester Cancer Center―Community Clinical Oncology Program

PURPOSE Sleep disruption is prevalent in patients with cancer and survivors, but the prevalence of insomnia, a distressing sleep disorder, in these populations has yet to be determined in large-scale studies. PATIENTS AND METHODS A total of 823 patients with cancer receiving chemotherapy (mean age, 58 years; 597 female patients) reported on sleep difficulties in a prospective study. RESULTS During day 7 of cycle 1 of chemotherapy, 36.6% (n = 301) of the patients with cancer reported insomnia symptoms, and 43% (n = 362) met the diagnostic criteria for insomnia syndrome. Patients with cancer younger than 58 years were significantly more likely to experience either symptoms of insomnia or insomnia syndrome (chi(2) = 13.6; P = .0002). Patients with breast cancer had the highest number of overall insomnia complaints. A significant positive association was found between symptoms of insomnia during cycles 1 and 2 of chemotherapy (phi = .62, P < .0001), showing persistence of insomnia during the first two cycles of chemotherapy. Sixty percent of the patient sample reported that their insomnia symptoms remained unchanged from cycle 1 to cycle 2. Those with insomnia complaints had significantly more depression and fatigue than good sleepers (all P < .0001). CONCLUSION The proportions of patients with cancer in this sample reporting symptoms of insomnia and meeting diagnostic criteria for insomnia syndrome during chemotherapy are approximately three times higher than the proportions reported in the general population. Insomnia complaints persist throughout the second chemotherapy cycle for the majority of patients with cancer in this study. Insomnia is prevalent, underrecognized, undermanaged, and understudied among patients with cancer receiving chemotherapy.

Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial

BACKGROUND Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer. METHODS 420 women with breast cancer who were having two or more hot flashes per day were randomly assigned placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day by mouth in three divided doses for 8 weeks. Each patient kept a 1-week, self-report diary on the frequency, severity, and duration of hot flashes before the start of the study and during weeks 4 and 8 of treatment. Analyses were by intention to treat. FINDINGS Evaluable data were available on 371 participants at 4 weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at 8 weeks (113 placebo, 114 gabapentin 300 mg, and 120 gabapentin 900 mg). The percentage decreases in hot-flash severity score between baseline and weeks 4 and 8, respectively were: 21% (95% CI 12 to 30) and 15% (1 to 29) in the placebo group; 33% (23 to 43) and 31% (16 to 46) in the group assigned gabapentin 300 mg; and 49% (42 to 56) and 46% (34 to 58) in the group assigned gabapentin 900 mg. The differences between the groups were significant (p=0.0001 at 4 weeks and p=0.007 at 8 weeks by ANCOVA for overall treatment effect, adjusted for baseline values); only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity. INTERPRETATION Gabapentin is effective in the control of hot flashes at a dose of 900 mg/day, but not at a dose of 300 mg/day. This drug should be considered for treatment of hot flashes in women with breast cancer.

Acupuncture-point stimulation for chemotherapy- induced nausea and vomiting

PURPOSE Assess the effectiveness of acupuncture-point stimulation on acute and delayed chemotherapy-induced nausea and vomiting in cancer patients. MATERIALS AND METHODS Randomized trials of acupuncture-point stimulation by needles, electrical stimulation, magnets, or acupressure were retrieved. Data were provided by investigators of the original trials and pooled using a fixed-effects model. RESULTS Eleven trials (N = 1,247) were pooled. Overall, acupuncture-point stimulation reduced the proportion of acute vomiting (relative risks [RR] = 0.82; 95% CI, 0.69 to 0.99; P = .04), but not the mean number of acute emetic episodes or acute or delayed nausea severity compared with controls. By modality, stimulation with needles reduced the proportion of acute vomiting (RR = 0.74; 95% CI, 0.58 to 0.94; P = .01), but not acute nausea severity. Electroacupuncture reduced the proportion of acute vomiting (RR = 0.76; 95% CI, 0.60 to 0.97; P = .02), but manual acupuncture did not; delayed symptoms were not reported. Acupressure reduced mean acute nausea severity (standardized mean difference = -0.19; 95% CI, -0.38 to -0.01; P = .03) and most severe acute nausea, but not acute vomiting or delayed symptoms. Noninvasive electrostimulation showed no benefit for any outcome. All trials used concomitant pharmacologic antiemetics, and all, except electroacupuncture trials, used state-of-the-art antiemetics. CONCLUSION This review complements data on postoperative nausea and vomiting, suggesting a biologic effect of acupuncture-point stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced acute vomiting, but studies with state-of-the-art antiemetics as well as studies for refractory symptoms are needed to determine clinical relevance. Acupressure seems to reduce chemotherapy-induced acute nausea severity, though studies did not involve a placebo control. Noninvasive electrostimulation seems unlikely to have a clinically relevant impact when patients are given state-of-the-art pharmacologic antiemetic therapy.

Effect of paroxetine hydrochloride (Paxil®) on fatigue and depression in breast cancer patients receiving chemotherapy

SummaryBackground. Fatigue can significantly interfere with a cancer patient’s ability to fulfill daily responsibilities and enjoy life. It commonly co-exists with depression in patients undergoing chemotherapy, suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue. Methods. We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy randomly assigned to receive either 20 mg of the selective serotonin re-uptake inhibitor (SSRI) paroxetine (Paxil®, SmithKline Beecham Pharmaceuticals) or an identical-appearing placebo. Patients began their study medication seven days following their first on-study treatment and continued until seven days following their fourth on-study treatment. Seven days after each treatment, participants completed questionnaires measuring fatigue (Multidimensional Assessment of Fatigue, Profile of Mood States-Fatigue/Inertia subscale and Fatigue Symptom Checklist) and depression (Profile of Mood States-Depression subscale [POMS-DD] and Center for Epidemiologic Studies-Depression [CES-D]). Results. Repeated-measures ANOVAs, after controlling for baseline measures, showed that paroxetine was more effective than placebo in reducing depression during chemotherapy as measured by the CES-D (p=0.006) and the POMS-DD (p=0.07) but not in reducing fatigue (all measures, ps > 0.27). Conclusions. Although depression was significantly reduced in the 44 patients receiving paroxetine compared to the 50 patients receiving placebo, indicating that a biologically active dose was used, no significant differences between groups on any of the measures of fatigued were observed. Results suggest that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment.

Nausea and Vomiting Remain a Significant Clinical Problem: Trends Over Time in Controlling Chemotherapy-Induced Nausea and Vomiting in 1413 Patients Treated in Community Clinical Practices

Data from 1413 outpatients in community-based clinical practices were collected in order to characterize the use and effectiveness of 5-HT(3) receptor antagonists for control of chemotherapy-induced nausea and vomiting (NV). Patients were divided by treatment starting date into six cohorts for trend analysis. In addition, NV symptoms were compared in 252 patients treated prior to the commercial introduction of the 5-HT(3) receptor antagonist antiemetics, and an equal number of patients treated after their introduction. A comparison of cohorts revealed a significant (P = 0. 027) downward trend over time for the frequency of post-treatment vomiting episodes, but not for frequency of post-treatment nausea (P = 0.69). The average duration of nausea following treatment increased significantly over time (P = 0.003). Although the introduction of 5-HT(3) receptor antagonist antiemetics has apparently led to a significant reduction in the frequency of post-treatment vomiting, there has been an accompanying increase in the duration of post-treatment nausea.

The effect of modafinil on cognitive function in breast cancer survivors

The authors conducted a randomized clinical trial examining the effects of modafinil in reducing persistent fatigue in patients after treatment for cancer and performed secondary analyses to assess the effect of modafinil on cognitive function.

The Efficacy of Acupressure and Acustimulation Wrist Bands for the Relief of Chemotherapy-Induced Nausea and Vomiting ☆: A University of Rochester Cancer Center Community Clinical Oncology Program Multicenter Study

As an adjunct to standard antiemetics for the relief of chemotherapy-induced nausea and vomiting (NV), 739 patients were randomly assigned to either: 1) acupressure bands, 2) an acustimulation band, or 3) a no band control condition. Patients in the acupressure condition experienced less nausea on the day of treatment compared to controls (P<0.05). There were no significant differences in delayed nausea or vomiting among the three treatment conditions. Additional analyses revealed pronounced gender differences. Men in the acustimulation condition, but not the acupressure condition, had less NV compared to controls (P<0.05). No significant differences among the three treatment conditions were observed in women, although the reduction in nausea on the day of treatment in the acupressure, compared to the no band condition, closely approached statistical significance (P=0.052). Expected efficacy of the bands was related to outcomes for the acupressure but not the acustimulation conditions.

Frequency, Severity, Clinical Course, and Correlates of Fatigue in 372 Patients during 5 Weeks of Radiotherapy for Cancer

Patients often describe fatigue as the most distressing of the symptoms they experienced during their cancer treatment. Fatigue may increase from initial levels experienced during cancer treatment with the addition of radiotherapy (RT).

Effect of gabapentin on nausea induced by chemotherapy in patients with breast cancer

In an anecdotal report, complete resolution of chemotherapy-induced nausea was seen in a patient with breast cancer, after she was placed on the anticonvulsant gabapentin. On this basis, we did an open-label study in which oral gabapentin 300 mg thrice daily was given for every other chemotherapy treatment in nine patients with breast cancer. Six of the nine reported at least a three-point improvement in peak delayed nausea (on an eight-point nausea scale), and three patients had complete resolution of nausea when taking gabapentin. This preliminary evidence shows that gabapentin might have a role in treatment of chemotherapy-induced nausea.