Phase II study of sequential chemotherapy with docetaxel|[ndash]|estramustine followed by mitoxantrone|[ndash]|prednisone in patients with advanced hormone-refractory prostate cancer

摘要

Sequential chemotherapy may improve treatment efficacy avoiding the additive toxicity associated with concomitant polichemotherapy in hormone-refractory prostate cancer (HRPC). Forty patients received docetaxel 30?mg?m?2 intravenous (i.v.), weekly, plus estramustine 280?mg twice daily for 12 weeks. After 2 weeks rest, patients with a decline or stable PSA were treated with mitoxantrone 12?mg?m?2 i.v. every 3 weeks plus prednisone 5?mg twice daily for 12 cycles. Forty patients were assessable for toxicity after docetaxel/estramustine. Main toxicities were grade 3–4 AST/ALT or bilirubin increase in seven patients (17.5%) and deep venous thrombosis (DVT) in four patients (10%). Twenty-seven patients received mitoxantrone/prednisone. Main toxicities included DVT in one patient (3.7%) and congestive heart failure in two patients (7%). Thirty-nine patients were assessable for PSA response. Twenty-nine patients (72.5%; 95% CI 63–82%) obtained a 50% PSA decline with 15 patients (37.5%; 95% CI 20–50%) that demonstrated a 90% decrease. Median progression-free and overall survival were respectively 7.0 (95% CI 5.8–8.2 months) and 19.2 months (95% CI 13.9–24.3 months). In conclusion, although this regimen demonstrated a favourable toxicity profile, sequential administration of mitoxantrone is not able to improve docetaxel activity in patients with HRPC.