Ulka N Vaishampayan1, Joseph Fontana2, Lance K Heilbrun3, Daryn Smith3, Elisabeth Heath2, Brenda Dickow4, William D Figg5. 1. Department of Oncology, Department of Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI. Electronic address: vaishamu@karmanos.org. 2. Department of Oncology, Department of Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI. 3. Biostatistics Core, Barbara Ann Karmanos Cancer Institute, Detroit, MI. 4. Clinical Trials Office, Barbara Ann Karmanos Cancer Institute, Detroit, MI. 5. Medical Oncology Branch, National Cancer Institute, Bethesda, MD.
Abstract
BACKGROUND: Satraplatin is an oral platinum compound that has demonstrated efficacy and tolerability in prostate cancer. Preclinical synergy between bevacizumab and platinum has been noted. METHODS: Docetaxel-pretreated metastatic castrate-resistant prostate cancer patients with disease progression were eligible. Satraplatin 80 mg/m(2) orally on days 1 to 5, prednisone 5mg twice daily, and bevacizumab 10mg/kg on day 1, and 15 mg/kg on day 15 were administered in 35-day cycles. RESULTS: Thirty one patients were enrolled. Grade 3 or 4 toxicities were pulmonary embolism in 2 patients and thrombocytopenia in 1 patient. 31% of the patients had a ≥ 30% decline in prostate-specific antigen. Median time to progression was 7.0 months (90% confidence interval [CI] 4.7-8.5mo) and median overall survival was 11.2 months (90% CI 9.1-16.4 mo). Polymorphism in the excision repair cross-complementation-1 (ERCC-1) gene was associated with time to progression (hazard ratio = 1.91). A circulating tumor cell count ≥ 5 was moderately prognostic of overall survival (hazard ratio = 1.49) as compared with CTC <5. CONCLUSIONS: The combination was tolerable, and revealed promising efficacy in metastatic castrate-resistant prostate cancer. ERCC1 genotype maybe predictive of clinical benefit with platinum-based therapy in metastatic prostate cancer.
BACKGROUND:Satraplatin is an oral platinum compound that has demonstrated efficacy and tolerability in prostate cancer. Preclinical synergy between bevacizumab and platinum has been noted. METHODS:Docetaxel-pretreated metastatic castrate-resistant prostate cancerpatients with disease progression were eligible. Satraplatin 80 mg/m(2) orally on days 1 to 5, prednisone 5mg twice daily, and bevacizumab 10mg/kg on day 1, and 15 mg/kg on day 15 were administered in 35-day cycles. RESULTS: Thirty one patients were enrolled. Grade 3 or 4 toxicities were pulmonary embolism in 2 patients and thrombocytopenia in 1 patient. 31% of the patients had a ≥ 30% decline in prostate-specific antigen. Median time to progression was 7.0 months (90% confidence interval [CI] 4.7-8.5mo) and median overall survival was 11.2 months (90% CI 9.1-16.4 mo). Polymorphism in the excision repair cross-complementation-1 (ERCC-1) gene was associated with time to progression (hazard ratio = 1.91). A circulating tumor cell count ≥ 5 was moderately prognostic of overall survival (hazard ratio = 1.49) as compared with CTC <5. CONCLUSIONS: The combination was tolerable, and revealed promising efficacy in metastatic castrate-resistant prostate cancer. ERCC1 genotype maybe predictive of clinical benefit with platinum-based therapy in metastatic prostate cancer.
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