Baseline quality of life as a prognostic indicator of survival: a meta-analysis of individual patient data from EORTC clinical trials.

BACKGROUND: Although individual studies show that baseline health-related quality of life (HRQOL) is a prognostic factor for survival, contradictory results have been published and very few meta-analyses have confirmed the finding. We examined whether HRQOL scores are associated with survival when pooled across a large sample of patients with different disease sites. METHODS: We selected 30 randomised controlled trials from the European Organisation for Research and Treatment of Cancer (EORTC) started between 1986 and 2004, which included survival data for 10 108 patients with 11 different cancer sites. Patients were eligible for inclusion if they had completed a baseline HRQOL assessment with the EORTC core quality of life questionnaire (QLQ-C30; n=7417). Sociodemographic variables were age (60 years) and sex (men vs women), and clinical variables were WHO performance status (0-1 vs 2-3), distant metastases (no vs yes), and cancer site. We assessed prognostic significance of sociodemographic and clinical variables and the 15 QLQ-C30 scales with Cox proportional hazard models. FINDINGS: In the stratified multivariate model including sociodemographic, clinical, and HRQOL data, the HRQOL parameters of physical functioning (hazard ratio 0.94, 95% CI 0.92-0.96; p<0.0001), pain (1.04, 1.02-1.06; p<0.0001), and appetite loss (1.05, 1.03-1.06; p<0.0001) provided significant prognostic information in addition to the parameters age (1.17, 1.06-1.28; p=0.0001), sex (0.74, 0.67-0.82; p<0.0001), and distant metastases (1.70, 1.49-1.93; p<0.0001), but not for WHO performance status (1.07, 0.97-1.19; p=0.11). Consideration of the three HRQOL parameters and sociodemographic and clinical data increased the predictive accuracy of prognosis of overall survival by 6% relative to sociodemographic and clinical characteristics alone (C statistic for concordance between predicted and observed overall survival 0.68 for sociodemographic and clinical variables, and 0.72 for sociodemographic, clinical, and HRQOL variables). INTERPRETATION: The results suggest that HRQOL scales provide prognostic information in addition to that of sociodemographic and clinical measures. This study shows that HRQOL data can help to predict survival in patients with cancer. FUNDING: Merck KGaA, EORTC Charitable Trust, and National Cancer Institute.

[Economic assessment of adjuvant and palliative chemotherapy in colorectal cancer: a review]. / Evaluation économique des chimiothérapies adjuvante et palliative dans le traitement du cancer colorectal: enseignements de la littérature.

The aim of this study is to perform a review of the literature on economic (or medico-economic) studies in the area of chemotherapy for colorectal cancer. French and international literature has been reviewed on this topic. Colorectal cancer represents a major public health problem due to high mortality, prevalence and costs. Up to now chemotherapy can be used at the adjuvant stage or at the palliative one. This work provides a synthesis of the main results of economic publications devoted to adjuvant and palliative chemotherapies, as well as a reflection on the limits frequently associated with such studies.

Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab.

PURPOSE: In this randomized, phase III study, quality of life (QoL) was assessed in patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) after high-dose radiotherapy alone or in combination with cetuximab. PATIENTS AND METHODS: Patients with stage III or IV nonmetastatic and measurable squamous cell carcinoma of the oropharynx, hypopharynx, or larynx were eligible. QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and EORTC QLQ Head and Neck Cancer-Specific Module at baseline, week 4, and at months 4, 8, and 12 postbaseline. RESULTS: In this study, one of the largest conducted in a population of patients with locoregionally advanced SCCHN, 424 patients received radiotherapy alone (213 patients) or radiotherapy plus cetuximab (211 patients). Radiotherapy/cetuximab significantly improved locoregional control (P = .005) and overall survival (P = .03) compared with radiotherapy alone, without significantly increasing radiotherapy-associated adverse events. The current analysis focused on the impact of cetuximab on the QoL. Compliance with completion of QoL questionnaires was high in both arms. QoL worsened during treatment and improved after cessation of treatment, reaching baseline levels at 12 months. There were no significant differences in QoL scores between the treatment arms. This was particularly notable for global health status/QoL, social functioning, social eating, and social contact. Pretreatment global health status/QoL was identified as a significant prognostic variable in these patients. CONCLUSION: The addition of cetuximab to radiotherapy significantly improved locoregional control and increased overall survival without adversely affecting QoL.

A critical review of pharmacoeconomic studies of acamprosate.

AIMS: This review assessed the published data on the cost-effectiveness of acamprosate for the treatment of alcohol dependence. METHODS: Four Markov modelling studies have assessed the therapeutic benefit and economic impact of acamprosate on the treatment of alcohol dependence. These have evaluated both short-term and long-term outcomes and have used German, Belgian, and Spanish costings. A fifth prospective cohort study collected real outcomes and data on expenditure during a 1 year study follow-up period. RESULTS: All five studies have produced consistent results, showing the use of acamprosate, which enhances abstinence rates, to reduce the total costs of treatment and thus be dominant over other rehabilitation strategies not involving pharmacotherapy. In all of the studies, the principal cost-driver is hospitalization. Although there is a short-term increase in treatment costs associated with drug acquisition, these are recovered from long-term savings attributable to reduced hospitalization and rehabilitation costs.

A pragmatic trial of acamprosate in the treatment of alcohol dependence in primary care.

AIMS: To assess the effectiveness of pharmacotherapy with acamprosate in alcohol-dependent patients treated in a naturalistic setting in primary care in France. METHODS: The ARES (Acamprosate et Repercussions Economiques et Sociales; Acamprosate and Economic and Social Repercussions) study was performed by 149 general practitioners interested in treating alcohol use disorders in France who included patients fulfilling DSM-IV criteria for alcohol dependence. The only exclusion criteria concerned contra-indications to acamprosate, co-medication with naltrexone and multiple substance abuse. Eligible patients were randomized to one of two treatment arms, either standard care alone or standard care with acamprosate, using an open-label design and followed up quarterly for a period of 1 year. The primary outcome variable was the change from baseline on the Alcohol-Related Problems Questionnaire. Secondary efficacy variables were abstinence, Clinical Global Impression, quality of life measured with the SF-36 and incidence of adverse events. An intent-to-treat population was used for outcome analysis. RESULTS: 422 patients were included, of whom 348 (82%) completed the protocol as planned. At the end of the study, patients randomized to the acamprosate group had significantly better outcomes in terms of total ARPQ score, change from baseline (-2.61 vs -3.44) and number of subjects with no alcohol-related problem. On average, patients treated with acamprosate had one less alcohol-related problem than did the controls. The number needed to treat in order to save one additional patient from alcohol-related problems compared to standard care was 7.14. Statistically significant differences in favour of the acamprosate group were observed for all secondary efficacy outcome measures including quality of life. CONCLUSIONS: Adjunctive therapy with acamprosate in primary care is associated with significantly better functional outcome. Pragmatic trials in alcohol dependence are both feasible and informative.