San Diego—A Veterans Administration (VA) Cooperative Study investigating chemotherapy after prostatectomy for high-risk prostate cancer (CSP #553) was underpowered to show a statistically significant benefit of early adjuvant chemotherapy versus observation as the standard of care in the primary endpoint analysis of progression-free survival (PFS).
The data analyses, however, showed a trend favoring treatment with docetaxel (Taxotere) plus prednisone. In addition, early adjuvant chemotherapy was well tolerated, and in pre-specified secondary analyses, it significantly prolonged PFS in men with high-stage (≥pT3b) prostate cancer and in African-Americans.
The findings were reported by Daniel W. Lin, MD, at the AUA annual meeting in San Diego.
“It is important to note that in the primary endpoint analysis, the magnitude of difference between the two treatment arms in this study is suggestive of significant antitumor activity for docetaxel and similar to that observed in other phase III trials,” said Dr. Lin, who is a study co-chair for CSP #553 and professor and chief of urologic oncology, University of Washington, Seattle. “In addition, the reason why the study was underpowered is that patient accrual was stopped before reaching the planned sample size due to resource limitations within the VA and not because of safety concerns.
“There are challenges for the treatment of high-risk prostate cancer because curative treatments, regardless of modality, are associated with a high recurrence rate. The data from CSP #553 clearly support ongoing and planned trials of systemic chemotherapy for hormone-sensitive prostate cancer.”
CSP #553 had a planned enrollment of 480 patients, but accrual was stopped after about 64 months when 297 patients had been randomized between observation (n=157) and chemotherapy with intravenous docetaxel, 75 mg once every 21 days for six cycles (n=140).
Men were eligible for enrollment if they had a histologic diagnosis of cT1-T2 prostate cancer prior to prostatectomy, an undetectable post-prostatectomy PSA, and any of the following high-risk findings: preoperative PSA >20.0 ng/mL, stage ≥pT3b, stage pT3a with Gleason grade 7-10, or stage pT2R1 with Gleason score 8-10. Node dissection at prostatectomy was mandated, and eligible men had to be node negative.
Patients were stratified prior to randomization based on PSA (>20.0 ng/mL vs. ≤20.0 ng/mL), Gleason score (8-10 vs. ≤7), tumor stage (≥pT3b vs. ≤pT3a), and surgical margin status (R1 vs. R0), and the two treatment arms were well matched for these clinical characteristics and in their demographics.