A double-blind, placebo-controlled, randomized trial of oral sodium clodronate for metastatic prostate cancer (MRC PR05 Trial).

Autor:	Dearnaley DP; Institute of Cancer Research and Royal Marsden Hospital, Sutton, UK., Sydes MR, Mason MD, Stott M, Powell CS, Robinson AC, Thompson PM, Moffat LE, Naylor SL, Parmar MK
Jazyk:	angličtina
Zdroj:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2003 Sep 03; Vol. 95 (17), pp. 1300-11.
DOI:	10.1093/jnci/djg038
Abstrakt:	Background: The most frequent site of metastases from prostate cancer is bone. Bisphosphonates reduce excessive bone turnover while preserving bone structure and mineralization in patients with other tumor types. We conducted a double-blind, placebo-controlled, randomized trial to determine whether the first-generation bisphosphonate sodium clodronate could improve bone progression-free survival (BPFS) times among men with bone metastases from prostate cancer. Methods: Between June 1994 and July 1998, 311 men who were starting or responding to first-line hormone therapy for bone metastases were randomly assigned to receive oral sodium clodronate (2080 mg/day) or placebo for a maximum of 3 years. The primary endpoint of the trial was symptomatic BPFS. Secondary endpoints included overall survival, treatment toxicity, and change in World Health Organization (WHO) performance status. Time-to-event data were analyzed using the log-rank chi-square test and Kaplan-Meier curves. All statistical tests were two-sided. Results: Baseline characteristics were balanced across the two groups. After a median follow-up of 59 months, the sodium clodronate group showed statistically nonsignificant better symptomatic BPFS (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.61 to 1.02; P =.066) and overall survival (HR = 0.80, 95% CI = 0.62 to 1.03; P =.082) than the control group. Patients in the clodronate group were less likely to have a worsened WHO performance status (HR = 0.71, 95% CI = 0.56 to 0.92; P =.008). However, the clodronate group reported more gastrointestinal problems and increased lactate dehydrogenase levels and required more frequent modification of the trial drug dose (HR for any adverse event = 1.71, 95% CI = 1.21 to 2.41; P =.002). Results of subgroup analyses suggested that clodronate might be more effective the sooner after diagnosis of metastatic bone disease it is started. Conclusion: These results suggest that further studies of the effect of newer generation bisphosphonates on BPFS in men with metastatic prostate cancer are warranted.
Databáze:	MEDLINE
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