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:


      • 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.



      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.


      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).


      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).


      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.

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        • Heidenreich A.
        • Bastian P.J.
        • Bellmunt J.
        • Bolla M.
        • Joniau S.
        • van der Kwast T.
        • et al.
        EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer.
        Eur Urol. 2014; 65: 467-479
        • Tannock I.F.
        • de Wit R.
        • Berry W.R.
        • Horti J.
        • Pluzanska A.
        • Chi K.N.
        • et al.
        Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer.
        N Engl J Med. 2004; 351: 1502-1512
        • Petrylak D.P.
        • Tangen C.M.
        • Hussain M.H.
        • Lara Jr., P.N.
        • Jones J.A.
        • Taplin M.E.
        • et al.
        Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer.
        N Engl J Med. 2004; 351: 1513-1520
        • Kantoff P.W.
        • Halabi S.
        • Conaway M.
        • Picus J.
        • Kirshner J.
        • Hars V.
        • et al.
        Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study.
        J Clin Oncol Off J Am Soc Clin Oncol. 1999; 17: 2506-2513
        • Berry W.
        • Dakhil S.
        • Modiano M.
        • Gregurich M.
        • Asmar L.
        Phase III study of mitoxantrone plus low dose prednisone versus low dose prednisone alone in patients with asymptomatic hormone refractory prostate cancer.
        J Urol. 2002; 168: 2439-2443
        • Oh W.K.
        • Manola J.
        • Babcic V.
        • Harnam N.
        • Kantoff P.W.
        Response to second-line chemotherapy in patients with hormone refractory prostate cancer receiving two sequences of mitoxantrone and taxanes.
        Urology. 2006; 67: 1235-1240
        • Berthold D.R.
        • Pond G.R.
        • de Wit R.
        • Eisenberger M.
        • Tannock I.F.
        Survival and PSA response of patients in the TAX 327 study who crossed over to receive docetaxel after mitoxantrone or vice versa.
        Ann Oncol Off J Eur Soc Med Oncol. 2008; 19: 1749-1753
        • de Bono J.S.
        • Oudard S.
        • Ozguroglu M.
        • Hansen S.
        • Machiels J.P.
        • Kocak I.
        • et al.
        Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial.
        Lancet (London, England). 2010; 376: 1147-1154
        • Scher H.I.
        • Fizazi K.
        • Saad F.
        • Taplin M.E.
        • Sternberg C.N.
        • Miller K.
        • et al.
        Increased survival with enzalutamide in prostate cancer after chemotherapy.
        N Engl J Med. 2012; 367: 1187-1197
        • Fizazi K.
        • Scher H.I.
        • Molina A.
        • Logothetis C.J.
        • Chi K.N.
        • Jones R.J.
        • et al.
        Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study.
        Lancet Oncol. 2012; 13: 983-992
        • Parker C.
        • Nilsson S.
        • Heinrich D.
        • Helle S.I.
        • O'Sullivan J.M.
        • Fossa S.D.
        • et al.
        Alpha emitter radium-223 and survival in metastatic prostate cancer.
        N Engl J Med. 2013; 369: 213-223
        • Kantoff P.W.
        • Higano C.S.
        • Shore N.D.
        • Berger E.R.
        • Small E.J.
        • Penson D.F.
        • et al.
        Sipuleucel-T immunotherapy for castration-resistant prostate cancer.
        N Engl J Med. 2010; 363: 411-422
        • Oh W.K.
        • Tay M.H.
        • Huang J.
        Is there a role for platinum chemotherapy in the treatment of patients with hormone-refractory prostate cancer?.
        Cancer. 2007; 109: 477-486
        • Oh W.K.
        • Halabi S.
        • Kelly W.K.
        • Werner C.
        • Godley P.A.
        • Vogelzang N.J.
        • et al.
        A phase II study of estramustine, docetaxel, and carboplatin with granulocyte-colony-stimulating factor support in patients with hormone-refractory prostate carcinoma: cancer and Leukemia Group B 99813.
        Cancer. 2003; 98: 2592-2598
        • Ross R.W.
        • Beer T.M.
        • Jacobus S.
        • Bubley G.J.
        • Taplin M.E.
        • Ryan C.W.
        • et al.
        A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel.
        Cancer. 2008; 112: 521-526
        • Reuter C.W.
        • Morgan M.A.
        • Ivanyi P.
        • Fenner M.
        • Ganser A.
        • Grunwald V.
        Carboplatin plus weekly docetaxel as salvage chemotherapy in docetaxel-resistant and castration-resistant prostate cancer.
        World J Urol. 2010; 28: 391-398
        • Hager S.
        • Ackermann C.J.
        • Joerger M.
        • Gillessen S.
        • Omlin A.
        Anti-tumour activity of platinum compounds in advanced prostate cancer-a systematic literature review.
        Ann Oncol Off J Eur Soc Med Oncol. 2016; 27: 975-984
        • Aparicio A.M.
        • Harzstark A.L.
        • Corn P.G.
        • Wen S.
        • Araujo J.C.
        • Tu S.M.
        • et al.
        Platinum-based chemotherapy for variant castrate-resistant prostate cancer.
        Clin Cancer Res Off J Am Assoc Cancer Res. 2013; 19: 3621-3630
        • Oudard S.
        • Kramer G.
        • Caffo O.
        • Creppy L.
        • Loriot Y.
        • Hansen S.
        • et al.
        Docetaxel rechallenge after an initial good response in patients with metastatic castration-resistant prostate cancer.
        BJU Int. 2015; 115: 744-752
        • Loriot Y.
        • Massard C.
        • Gross-Goupil M.
        • Di Palma M.
        • Escudier B.
        • Bossi A.
        • et al.
        The interval from the last cycle of docetaxel-based chemotherapy to progression is associated with the efficacy of subsequent docetaxel in patients with prostate cancer.
        Eur J Cancer (Oxford, England 1990). 2010; 46: 1770-1772
        • Bracarda S.
        • Caserta C.
        • Galli L.
        • Carlini P.
        • Pastina I.
        • Sisani M.
        • et al.
        Docetaxel rechallenge in metastatic castration-resistant prostate cancer: any place in the modern treatment scenario? An intention to treat evaluation.
        Future Oncol (London, England). 2015; 11: 3083-3090
        • Di Lorenzo G.
        • Buonerba C.
        • Faiella A.
        • Rescigno P.
        • Rizzo M.
        • Autorino R.
        • et al.
        Phase II study of docetaxel re-treatment in docetaxel-pretreated castration-resistant prostate cancer.
        BJU Int. 2011; 107: 234-239
        • Aparicio A.
        Advances in the understanding and treatment of AR-indifferent disease.
        ASCO 2017. February 16, 2017;
        • Eymard J.C.
        • Oudard S.
        • Gravis G.
        • Ferrero J.M.
        • Theodore C.
        • Joly F.
        • et al.
        Docetaxel reintroduction in patients with metastatic castration-resistant docetaxel-sensitive prostate cancer: a retrospective multicentre study.
        BJU Int. 2010; 106: 974-978
        • Caffo O.
        • Pappagallo G.
        • Brugnara S.
        • Caldara A.
        • di Pasquale M.C.
        • Ferro A.
        • et al.
        Multiple rechallenges for castration-resistant prostate cancer patients responding to first-line docetaxel: assessment of clinical outcomes and predictive factors.
        Urology. 2012; 79: 644-649
        • Heck M.M.
        • Thalgott M.
        • Retz M.
        • Wolf P.
        • Maurer T.
        • Nawroth R.
        • et al.
        Rational indication for docetaxel rechallenge in metastatic castration-resistant prostate cancer.
        BJU Int. 2012; 110: E635-E640
        • Sweeney C.J.
        • Chen Y.H.
        • Carducci M.
        • Liu G.
        • Jarrard D.F.
        • Eisenberger M.
        • et al.
        Chemohormonal therapy in metastatic hormone-sensitive prostate cancer.
        N Engl J Med. 2015; 373: 737-746
        • James N.D.
        • Sydes M.R.
        • Clarke N.W.
        • Mason M.D.
        • Dearnaley D.P.
        • Spears M.R.
        • et al.
        Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial.
        Lancet (London, England). 2016; 387: 1163-1177

      Linked Article

      • When and how to use carboplatin in metastatic castration-resistant prostate cancer?
        European Journal of CancerVol. 92
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          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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