Five-year relapse-free survival and predictors of relapse following preoperative docetaxel and mitoxantrone for high-risk localized prostate cancer
| Autor: | Paul H. Lange, Brooks L. S. Rademacher, Stephen Lieberman, Celestia S. Higano, N. Janeba, Tomasz M. Beer, Mark Garzotto, Ladan Fazli, Catherine A. O’Brien |
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| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 27:5121-5121 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2009.27.15_suppl.5121 |
| Popis: | 5121 Background: Efforts to incorporate systemic therapy with activity against castration-resistant prostate cancer into the early management of high-risk disease are motivated by persistent risk of relapse when neoadjuvant androgen suppression therapy (AST) is combined with surgery. As docetaxel and mitoxantrone exert anti-tumor effects through distinct cellular mechanisms, this combination has the potential for synergistic activity against prostate cancer. Here we report the 5-year outcomes of patients treated with a novel regimen that combines these agents without AST prior to prostatectomy. We also examined pathologic, biomarker and clinical predictors of early relapse. Methods: 57 high-risk prostate cancer patients were enrolled in a phase I/II study of weekly docetaxel 35 mg/m2 and escalating mitoxantrone to 4 mg/m2 delivered weekly for 3 of every 4 weeks per cycle for 4 cycles over 16 weeks followed by radical prostatectomy. A tissue micro-array constructed from the prostatectomy specimens served to facilitate the exploratory evaluation of biomarkers. The primary end point was relapse-free survival. Relapse was defined as a confirmed serum PSA > 0.4 ng/mL. Results: 54 of 57 pts received all 4 cycles of docetaxel and mitoxantrone prior to radical prostatectomy. Grade 4 toxicities were limited to leucopenia, neutropenia and hyperglycemia. Serum testosterone levels remained stable after chemotherapy. Negative surgical margins were attained in 67% of cases. Lymph node involvement was detected in 18.5% of cases. With a median follow-up of 63 months (range 7 to 86 months), 27 of 57 (47.4%) patients recurred. The Kaplan-Meier progression-free survival at 2 years was 65.5% (95% CI 53.0% to 78.0%) and 49.8% at 5 years (95% CI 35.5% to 64.1%). Pretreatment serum PSA, lymph node involvement, and post-chemotherapy tissue VEGF expression were independent predictors of early relapse. Conclusions: Preoperative combination chemotherapy with docetaxel and mitoxantrone is safe. Approximately half of the high risk pts remain relapse free at 5 years and clinical and molecular predictors of early relapse in this population have been identified. [Table: see text] |
| Databáze: | OpenAIRE |
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