Phase III double-blind, placebo-controlled study of gabapentin for the prevention of delayed chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy, NCCTG N08C3 (Alliance).

BACKGROUND: Despite targeted antiemetics, data support an unmet need related to the management of delayed nausea and vomiting (NV). Promising pilot data informed this phase III trial evaluating gabapentin for delayed NV from highly emetogenic chemotherapy (HEC). METHODS: Participants were randomized to receive prophylactic treatment with 20 mg of dexamethasone and a 5HT3 receptor antagonist (RA) on the day of chemotherapy, followed by gabapentin 300 mg twice a day and dexamethasone (dex) or placebo and dex after HEC. Gabapentin/placebo was started the day of chemotherapy and continued through day 5 for the first chemotherapy cycle, whereas dex was titrated down on days 2-4. The primary end point was complete response (CR), defined as no emesis and no use of rescue medications on days 2-6, using an NV diary. The percentages of those in each group with a CR were compared by Fisher's exact test. RESULTS: Four hundred thirty patients were enrolled in this study. Forty-seven percent of patients in the gabapentin arm and 41% in the placebo arm had a CR (P = .23). Mean number of emesis episodes was <0.5 daily, and mean nausea severity was < 2 (mild). In both arms, patient satisfaction with NV control was greater than 8 (with 10 being perfectly satisfied). There were no significant differences in unwanted side effects. CONCLUSIONS: In this study, gabapentin did not significantly improve delayed NV. Patients were satisfied with the control of their nausea and vomiting irrespective of arm. The use of a 5HT3 RA and dexamethasone provided good control of nausea and vomiting for most patients.

The relation between cancer patient treatment decision-making roles and quality of life.

BACKGROUND: The objective of this study was to explore relations between patient role preferences during the cancer treatment decision-making process and quality of life (QOL). METHODS: One-year cancer survivors completed a survey in 2000 as part of a larger survey conducted by the American Cancer Society. The current report was based on survey respondents from Minnesota (response rate, 37.4%). Standardized measures included the Profile of Mood States (scores were converted to have a range, from 0 to 100, with 100 indicating the best mood), the Medical Outcomes Survey 36-item short-form health survey (SF-36) (standardized scores), and the Control Preferences Scale. Patients' actual and preferred role preference distributions and concordance between roles were compared with QOL scores using 2-sample t test methodology. RESULTS: The actual role of survivors (n = 594) in cancer care was 33% active, 50% collaborative, and 17% passive. Their preferred role was 35% active, 53% collaborative, and 13% passive. Overall, 88% of survivors had concordant preferred and actual roles. Survivors who had concordant roles had higher SF-36 Physical Component Scale (PCS) scores (P < .01), higher vitality (P = .01), less fatigue (P < .01), less confusion (P = .01), less anger (P = .046), and better overall mood (P = .01). These results were similar among both women and younger individuals (aged <60 years). Survivors who had active actual roles had higher PCS scores (P < .01), less tension (P = .04), and higher vitality (P = .04) than survivors who were either collaborative or passive. No differences existed in QOL scores according to preferred role. CONCLUSIONS: Survivors who experienced discordance between their actual role and their preferred role reported substantial QOL deficits in both physical and emotional domains. These results indicate the need to support patient preferences.

Randomized controlled trial of acitretin versus placebo in patients at high-risk for basal cell or squamous cell carcinoma of the skin (North Central Cancer Treatment Group Study 969251).

BACKGROUND: Chemoprevention with systemic retinoids has demonstrated promise in decreasing the incidence of new primary nonmelanoma skin cancers (NMSCs) in immunocompromised post-transplantation recipients. There is limited evidence for the use of systemic retinoids in the nontransplantation patient. To the authors' knowledge, this is the first randomized controlled trial to assess the efficacy of acitretin as a chemopreventive agent in nontransplantation patients at high-risk for NMSC. METHODS: The study was designed as a prospective, randomized, double-blind, placebo-controlled clinical trial. To test the possible skin cancer-preventing effect of a 2-year treatment with acitretin, 70 nontransplantation patients aged ≥18 years who had a history of ≥2 NMSCs within 5 years of trial onset were randomized to receive either placebo or acitretin 25 mg orally 5 days per week. The primary outcome measure was the rate of new NMSC development. RESULTS: Seventy patients were randomized to receive either acitretin alone (N = 35) or placebo (N = 35). During the 2-year treatment period, the patients who received acitretin did not have a statistically significant reduction in the rate of new primary NMSCs (odds ratio, 0.41; 95% confidence interval, 0.15-1.13; 54% vs 74%; P = .13). However, using the incidence of new NMSC, the time to new NMSC, and total NMSC counts, an umbrella test indicated a significant trend that favored the use of acitretin (chi-square statistic, 3.94; P = .047). The patients who received acitretin reported significantly more mucositis and skin toxicities compared with the patients who received placebo. CONCLUSIONS: Although there was not a statistically significant benefit observed with the use of acitretin, this may have been the result of low statistical power.

Preferred roles in treatment decision making among patients with cancer: a pooled analysis of studies using the Control Preferences Scale.

OBJECTIVES: To collect normative data, assess differences between demographic groups, and indirectly compare US and Canadian medical systems relative to patient expectations of involvement in cancer treatment decision making. STUDY DESIGN: Meta-analysis. METHODS: Individual patient data were compiled across 6 clinical studies among 3491 patients with cancer who completed the 2-item Control Preferences Scale indicating the roles they preferred versus actually experienced in treatment decision making. RESULTS: The roles in treatment decision making that patients preferred were 26% active, 49% collaborative, and 25% passive. The roles that patients reported actually experiencing were 30% active, 34% collaborative, and 36% passive. Roughly 61% of patients reported having their preferred role; only 6% experienced extreme discordance between their preferred versus actual roles. More men than women (66% vs 60%, P = .001) and more US patients than Canadian patients (84% vs 54%, P <.001) reported concordance between their preferred versus actual roles. More Canadian patients than US patients preferred and actually experienced (42% vs 18%, P <.001) passive roles. More women than men reported taking a passive role (40% vs 24%, P <.001). Older patients preferred and were more likely than younger patients to assume a passive role. CONCLUSIONS: Roughly half of the studied patients with cancer indicated that they preferred to have a collaborative relationship with physicians. Although most patients had the decision-making role they preferred, about 40% experienced discordance. This highlights the need for incorporation of individualized patient communication styles into treatment plans.

Phase III, placebo-controlled trial of three doses of citalopram for the treatment of hot flashes: NCCTG trial N05C9.

PURPOSE: Up to 75% of women experience hot flashes, which can negatively impact quality of life. As hot flash physiology is not definitively understood, it cannot be assumed that effective agents represent class effects. Therefore, there is a continued need for rigorous evaluation to identify effective nonhormonal options for hot flash relief. METHODS: A randomized, double-blind trial evaluated citalopram at target doses of 10, 20, or 30 mg/d versus placebo for 6 weeks. Postmenopausal women with at least 14 bothersome hot flashes per week recorded hot flashes for 7 days before starting treatment and were then titrated to their target doses. The primary end point was the change from baseline to 6 weeks in hot flash score. RESULTS: Two hundred fifty-four women were randomly assigned onto this study. Data for hot flash scores and frequencies showed significant improvement in hot flashes with citalopram over placebo, with no significant differences among doses. Reductions in mean hot flash scores were 2.0 (23%), 7.0 (49%), 7.7 (50%), and 10.7 (55%) for placebo and 10, 20, and 30 mg of citalopram, respectively (P

Newer antidepressants and gabapentin for hot flashes: an individual patient pooled analysis.

PURPOSE: Nonhormonal treatment options have been investigated as treatments for hot flashes, a major clinical problem in many women. Starting in 2000, a series of 10 individual double-blind placebo-controlled studies has evaluated newer antidepressants and gabapentin for treating hot flashes. This current project was developed to conduct an individual patient pooled analysis of the data from these published clinical trials. PATIENTS AND METHODS: Individual patient data were collected from the various study investigators who published their study results between 2000 and 2007. Between-study heterogeneity for study characteristics and patient populations was tested via chi2 tests before a pooled analysis. The primary end point, the change in hot flash activity from baseline to week 4, for each agent was calculated via both weighted and unweighted approaches, using the size of the study as the weight. Basic summary statistics were produced for hot flash score and frequency using the following three statistics: raw change, percent reduction, and whether or not a 50% reduction was achieved. RESULTS: This study included seven trials of newer antidepressants and three trials of gabapentin. The optimal doses (defined by individual study results) of the newer antidepressants paroxetine, venlafaxine, fluoxetine, and sertraline decreased hot flash scores by 41%, 33%, 13%, and 3% to 18% compared with the corresponding placebo arms, respectively. The three gabapentin trials decreased hot flashes by 35% to 38% compared with the corresponding placebo arms. CONCLUSION: Some newer antidepressants and gabapentin, within 4 weeks of therapy initiation, decrease hot flashes more than placebo.

Newer antidepressants and gabapentin for hot flashes: a discussion of trial duration.

OBJECTIVE: Information regarding the ideal length of hot flash trials is scarce. In the literature, hot flash trial durations have commonly varied from 4 to 12 weeks. This article is devoted to providing scientific data to better ascertain how long it is necessary to conduct hot flash trials with newer centrally acting agents. METHODS: Individual participant data were collected from all known published, through December 2007, randomized, placebo-controlled, double-blinded clinical trials regarding the use of newer antidepressants and gabapentin for hot flash relief. Trials that studied periods longer than 4 weeks were included for this project. Profile analysis was applied to the hot flash activity longitudinal data for each study individually, allowing a comparison of data collected for 6 to 12 treatment weeks versus data collected for only 4 treatment weeks. RESULTS: Ten studies were identified, five of them fulfilled the eligibility criteria for this investigation, three evaluating gabapentin, and two newer antidepressants. Flatness tests from a profile analysis did not provide any evidence that hot flash activity increased or decreased between week 4 and time periods up to 12 weeks. CONCLUSIONS: Changes in hot flash scores from newer antidepressants and gabapentin are apparent within 4 weeks of therapy. Available data indicate that hot flash treatment efficacy, compared with that of placebo, remains stable for up to 12 weeks of follow-up.