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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Article info
Publication history
Published online: December 18, 2017
Accepted:
November 20,
2017
Received in revised form:
November 9,
2017
Received:
July 14,
2017
Identification
Copyright
© 2017 Elsevier Ltd. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- When and how to use carboplatin in metastatic castration-resistant prostate cancer?European Journal of CancerVol. 92
- PreviewFor 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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