Annals of Oncology Advance Access originally published online on January 24, 2005
Annals of Oncology 2005 16(3):419-424; doi:10.1093/annonc/mdi096
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© 2005 European Society for Medical Oncology
Sequential mitoxantrone/prednisone followed by docetaxel/estramustine in patients with hormone refractory metastatic prostate cancer: results of a phase II study
1 Medical Oncology Service, Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Badalona, Barcelona; 2 Medical Oncology Service, Hospital Universitario Insular de Gran Canaria, Las Palmas; 3 Medical Oncology Service, Complexo Hospitalario de Pontevedra, Pontevedra; 4 Hospital del Espiritu Santo, Santa Coloma de Grament, Barcelona; 5 Urology Department, Hospital Germans Trias i Pujol, Badalona, Barcelona; 6 Autonomous University of Madrid, Red de Centros de Epidemiologia y Salod Pública (RCESP), Madrid, Spain
* Correspondence to: Dr A. Font, Medical Oncology Service, Institut Català d'Oncologia, Hospital Germans Trias I Pujol, Carretera del Canyet s/n, 08916 Badalona, Barcelona, Spain. Tel: +34-93-4978925; Fax: +34-93-4978950; Email: afont{at}ns.hugtip.scs.es
Background: Mitoxantrone/prednisone ameliorates symptoms in hormone refractory prostate cancer (HRPC) but has no effect on survival. Docetaxel (Taxotere)/estramustine improves response but with significant toxicity. We reasoned that a sequential administration of the two regimens could be a viable alternative for delivering full doses of chemotherapy, avoiding overlapping toxicity and preserving dose intensity.
Patients and methods: Thirty HRPC patients were treated with mitoxantrone 10 mg/m2, day 1, every 3 weeks, plus prednisone 5 mg twice daily, for three cycles, followed by estramustine phosphate, 280 mg three times daily, days 1 to 5, plus docetaxel 75 mg/m2, day 2, every 3 weeks for a maximum of 10 cycles.
Results: All patients were assessable for response and toxicity. After mitoxantrone/prednisone treatment, the prostate-specific antigen (PSA) response rate was 23%, which increased to 63% after completion of sequential mitoxantrone/prednisone and docetaxel/estramustine treatment (12 partial and 7 complete responses). With a median follow-up of 18 months, median survival for all patients was 18 months, and median progression-free survival was 10 months. The mitoxantrone/prednisone regimen was well tolerated, and the only grade 3–4 toxicity was grade 3 neutropenia in four (13%) patients. Twenty-nine patients received a total of 173 cycles of docetaxel/estramustine (median, 6 cycles/patient). Six (20%) patients had grade 3–4 neutropenia and two (6%) patients had febrile neutropenia episodes. The most frequent non-hematological toxic effects were asthenia, nausea and vomiting, edemas and onycholysis. Two (6%) patients had deep venous thrombosis.
Conclusions: Mitoxantrone/prednisone followed by docetaxel/estramustine is a well-tolerated and active regimen in HRPC. Sequential therapy is feasible and can be used to integrate novel, more active regimens.
Key words: docetaxel, mitoxantrone, prostate cancer, sequential, efficacy