BERKELEY, CA (UroToday.com) - Clinical trials rely on accurate measures correlating disease progression and patient survival. The Response Evaluation Criteria in Solid Tumors (RECIST) do not necessarily correlate well with clinical manifestations of prostate cancer (CaP). In the March 1, 2007 issue of Clinical Cancer Research, Dr. Howard Scher and colleagues at Memorial Sloan-Kettering Cancer Center and Cornell University report on correlations of progression-free survival (PFS) and overall survival (OS) in patients treated with microtubule-targeted treatments.

The authors hypothesize that the measure that a drug has not worked is best represented by PFS, considered as the time from the start of treatment to progression of disease, death, or last follow-up. They feel that PFS would be an intermediate endpoint with a stronger association with survival. They explored this concept by studying the PFS and OS of patients with metastatic CaP who have undergone androgen-deprivation therapy (ADT) and were enrolled in 3 studies of microtubule-targeted cytotoxic agents. The study included; 40 men treated with docetaxel/estramustine/carboplatin, 24 patients treated with docetaxel/intravenous estramustine and carboplatin, and 52 men treated with epothilone B with or without estramustine. Ultimately, 95 men had data appropriate for analysis.

The relationship between PFS and survival time was moderate. The concordance between PFS and OS was 0.40 when using radiographic PFS and 0.33 when using PSA PFS. The relationship between radiographic PFS and OS events were weakest for the early progression-free events. In 20% of cases, radiographic progression-free events were recorded at the time of the first scheduled scan, within 3 months from the start of treatment. This suggests that these progressions occurred prior to the first post-treatment scan, and thus resulted in a significant loss of information. The PSA PFS and OS correlation was weaker in the later follow-up period. The researchers hypothesize that the 3 PSA increases prior to enrollment in the trial were an indication of aggressive CaP and provided a moderate mirror for the time of death. On the other hand, PSA increases later in the follow-up period reflected less aggressive disease and the OS in these men was affected by a multitude of factors. The resulted in a reduction in the association measure in later follow-up.

The authors suggest that reliance on an endpoint that is moderately associated with OS may result in failure to recognize potentially useful therapies or the investment of significant resources into a therapy that does not have a substantive effect on OS.

Howard I. Scher, Mary Warren, and Glenn Heller

Clin Cancer Res 2007; 13(5):1488-92

UroToday.com Prostate Cancer Section

Written by Christopher P. Evans, MD, a Contributing Editor with UroToday.

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