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A randomised phase II trial of docetaxel versus docetaxel plus carboplatin in patients with castration-resistant prostate cancer who have progressed after response to prior docetaxel chemotherapy: The RECARDO trial

Published:December 18, 2017DOI:https://doi.org/10.1016/j.ejca.2017.11.021

      Highlights

      • Re-treatment with docetaxel monotherapy is safe and effective in selected patients.
      • The median progression-free survival in this group was 12.7 months.
      • Addition of carboplatin does not improve the progression-free or overall survival.
      • Addition of carboplatin resulted in more gastrointestinal and infectious adverse events.

      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 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.

      Keywords

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      Linked Article

      • When and how to use carboplatin in metastatic castration-resistant prostate cancer?
        European Journal of CancerVol. 92
        • Preview
          For metastatic castration-resistant prostate cancer (mCRPC), docetaxel was the first drug to show an overall survival (OS) benefit in two large phase III trials published in 2004 [1,2]. Until 2010 when cabazitaxel and abiraterone were shown to prolong survival after first-line docetaxel chemotherapy, physicians had very little treatment options to offer for men with mCRPC, and docetaxel re-challenge was frequently used despite the lack of prospective trial data [3,4].
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