Jane T. Hickok

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.

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.

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 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).

Frequency and correlates of fatigue in lung cancer patients receiving radiation therapy: Implications for management

The medical records of 50 consecutive patients receiving radiation therapy for histologically diagnosed lung cancer were retrospectively reviewed to determine the frequency of fatigue and its relationship to pain, depression, and other potentially treatable correlates. Fatigue developed in 39 of the 50 patients (78%), and was not strongly related to demographic or disease variables. Pain was experienced by 40 patients (80%), but depression was noted in the records of only six patients (12%). Onset of fatigue closely followed development of pain in only 11 patients. Lower frequency of fatigue in patients with previous surgery or chemotherapy and the likelihood of a response shift suggest these were not significant causes of fatigue. Previous studies highlight a higher frequency of depression in cancer patients and a correlation with treatment-related fatigue. Prospective studies on the relationship between depression and fatigue and the ability of antidepressants to ameliorate treatment-related fatigue are needed.

5-Hydroxytryptamine-receptor antagonists versus prochlorperazine for control of delayed nausea caused by doxorubicin: a URCC CCOP randomised controlled trial.

BACKGROUND Despite widespread use of short-acting antagonists for the 5-hydroxytryptamine (5-HT) receptor, about 50% of patients given moderately emetogenic chemotherapy have delayed nausea. We aimed to assess whether a 5-HT-receptor antagonist was more effective than was prochlorperazine for control of delayed nausea and delayed vomiting caused by doxorubicin. METHODS 691 patients who previously had not had chemotherapy and who were scheduled to receive doxorubicin were given a short-acting 5-HT-receptor antagonist and dexamethasone before doxorubicin (day 1), and were randomly assigned to one of three regimens for days 2 and 3: 10 mg prochlorperazine taken orally every 8 h; any first-generation 5-HT-receptor antagonist (except palonosetron) taken as standard dose intravenously or orally; or 10 mg prochlorperazine taken as needed. Nausea and vomiting were assessed by use of a home record. The primary endpoint was mean severity of delayed nausea. The secondary endpoint was quality of life. Analyses were done by intention to treat. FINDINGS 519 (77%) of the 671 evaluable patients had delayed nausea, with a mean severity of 3.33 (95% CI 3.22-3.44). 161 (71%) of 226 patients assigned prochlorperazine every 8 h reported delayed nausea (mean severity 3.37 [3.16-3.58]), as did 179 (79%) of 226 patients assigned 5-HT-receptor antagonists (3.29 [3.09-3.48]) and 179 (82%) of 219 patients assigned prochlorperazine as needed (3.33 [3.15-3.50]); groups did not differ in mean severity (p=0.853, one-way ANOVA). Patients allocated prochlorperazine every 8 h had less delayed nausea than did those allocated 5-HT-receptor antagonists (p=0.05, t test) and those allocated prochlorperazine as needed (p=0.009, t test). INTERPRETATION Short-acting 5-HT-receptor antagonists are no better than is prochlorperazine in control of delayed nausea caused by doxorubicin. Although fewer patients taking prochlorperazine report delayed nausea, the proportion was unacceptably high.

Nausea and emesis: evidence for a biobehavioral perspective

Abstract For most people, nausea and vomiting (NV) are simply unfortunate consequences of overindulgent college days or overenthusiastic amusement rides. Yet for most cancer patients, nausea and vomiting (also referred to as emesis) remain among the most frequent side effects of cancer chemotherapy. Patients typically view control of nausea as more important than control of emesis, while physicians and nurses judge emesis control to be more important to antiemetic efficacy than nausea control. The 5-HT3 receptor antagonists have been shown to be clinically more effective in controlling emesis, particularly that caused by regimens containing high-dose cisplatin, than previously available agents. Disappointingly, however, these drugs do not appear to be more effective than previous antiemetics in reducing nausea. In addition, the 5-HT3 receptor antagonists may become less effective over repeated chemotherapy administrations, and they remain expensive. An impediment to research progress has been an insularity that has prompted two parallel research efforts: one searching for biological understanding to enhance pharmacological intervention(s) and the other searching for psychological understanding to aid in developing more effective behavioral intervention(s). While both approaches have been successful, it is time to have the two views merge into a biobehavioral framework that combines them both. This paper draws on both physiological and psychological origins of NV to begin the development of a biobehavioral model of development that integrates features of both approaches.

Sources of information used by patients to learn about chemotherapy side effects.

BACKGROUND Little is known about the relative importance of specific information sources patients use to obtain knowledge about treatment side effects. The authors examined information sources used to learn about side effects, why patients believe they will experience some but not others, and the meanings side effects have in terms of treatment efficacy. METHODS Before treatment, 31 ovarian cancer patients and 81 men and women with a variety of cancer diagnoses completed a questionnaire assessing their expectations about experiencing specific side effects of chemotherapy and information sources used. RESULTS The doctor or nurse was the most frequently cited source of side-effect information, with readings second. While most thought they would get certain side effects because the doctor or nurse had said so, most instinctively believed they would not get others. CONCLUSIONS Patients relied on medical and non-medical information sources. Further research could examine other sources for their influences on information-seeking activities.