Esther W Bouman-Wammes1, H Pieter van den Berg2, Linda de Munck3, Aart Beeker4, Carolien H Smorenburg5, Walter L Vervenne6, Juleon L L M Coenen7, Henk M W Verheul8, Winald R Gerritsen9, Alfons J M Van den Eertwegh8. 1. Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: e.bouman@vumc.nl. 2. Department of Medical Oncology, Tergooi Hospital, Hilversum, The Netherlands. 3. Department of Research, Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands. 4. Department of Medical Oncology, Spaarne Gasthuis, Hoofddorp, The Netherlands. 5. Department of Medical Oncology, Antoni van Leeuwenhoek, Amsterdam, The Netherlands. 6. Department of Medical Oncology, Deventer ziekenhuis, Deventer, The Netherlands. 7. Department of Medical Oncology, Isala kliniek, Zwolle, The Netherlands. 8. Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. 9. Department of Medical Oncology, Radboud UMC, Nijmegen, The Netherlands.
Abstract
BACKGROUND:Docetaxel is standard first-line chemotherapy for patients with metastatic castration-resistant prostate carcinoma (mCRPC). Docetaxel re-challenge has never been tested in a prospective randomised controlled study. As some studies support the addition of carboplatin to docetaxel, we performed a phase II trial investigating the combination of docetaxel plus carboplatin versus docetaxel re-treatment in docetaxel pre-treated mCRPC patients. METHODS:Patients with mCRPC with a progression-free interval of ≥3 months after initialdocetaxel treatment were randomised between docetaxel 75 mg/m2 or docetaxel 60 mg/m2 plus carboplatin AUC4. The primary end-point was progression-free survival (PFS; PSA/RECIST). RESULTS: Owing to insufficient recruitment, the study was discontinued early after inclusion of 75 patients (targeted 150) PFS and overall survival (OS) were comparable between both groups (median PFS 12.7 months (95% CI 9.9-17.5 months) with docetaxel monotherapy and 11.7 months (95% CI 8.5-21.0 months) with combination therapy (p = 0.98); OS 18.5 months (95% CI 11.8-24.5 months) versus 18.9 months (95% CI 16.0-23.7 months) (p = 0.79). An interim analysis (SEQTEST) showed that the null hypothesis could already be excepted, and no significant difference between both study arms was expected if inclusion would be completed. The incidence of grade 3-4 infections and gastrointestinal side-effects was numerical higher in the carboplatin arm (p = 0.056). CONCLUSION: This early terminated study suggests no benefit from the addition of carboplatin to docetaxel re-treatment in patients with mCRPC, whereas the combination resulted in more toxicity. Re-treatment with docetaxel monotherapy appears to be feasible, save and effective for patients with mCRPC and an initial good response to docetaxel. TRIAL REGISTRATION: NTR3070.
RCT Entities:
BACKGROUND:Docetaxel is standard first-line chemotherapy for patients with metastatic castration-resistant prostate carcinoma (mCRPC). Docetaxel re-challenge has never been tested in a prospective randomised controlled study. As some studies support the addition of carboplatin to docetaxel, we performed a phase II trial investigating the combination of docetaxel plus carboplatin versus docetaxel re-treatment in docetaxel pre-treated mCRPC patients. METHODS:Patients with mCRPC with a progression-free interval of ≥3 months after initial docetaxel treatment were randomised between docetaxel 75 mg/m2 or docetaxel 60 mg/m2 plus carboplatin AUC4. The primary end-point was progression-free survival (PFS; PSA/RECIST). RESULTS: Owing to insufficient recruitment, the study was discontinued early after inclusion of 75 patients (targeted 150) PFS and overall survival (OS) were comparable between both groups (median PFS 12.7 months (95% CI 9.9-17.5 months) with docetaxel monotherapy and 11.7 months (95% CI 8.5-21.0 months) with combination therapy (p = 0.98); OS 18.5 months (95% CI 11.8-24.5 months) versus 18.9 months (95% CI 16.0-23.7 months) (p = 0.79). An interim analysis (SEQTEST) showed that the null hypothesis could already be excepted, and no significant difference between both study arms was expected if inclusion would be completed. The incidence of grade 3-4 infections and gastrointestinal side-effects was numerical higher in the carboplatin arm (p = 0.056). CONCLUSION: This early terminated study suggests no benefit from the addition of carboplatin to docetaxel re-treatment in patients with mCRPC, whereas the combination resulted in more toxicity. Re-treatment with docetaxel monotherapy appears to be feasible, save and effective for patients with mCRPC and an initial good response to docetaxel. TRIAL REGISTRATION: NTR3070.
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