First- and second-line chemotherapy with docetaxel or mitoxantrone in patients with hormone-refractory prostate cancer (HRPC): Does sequence matter?

Abstract

4611 Background: Docetaxel (D) is considered the first-line treatment in patients (pts) with HRPC. It is unknown whether mitoxantrone (M) in patients who have failed first-line docetaxel remains a viable option for palliation or if docetaxel in patients who failed a less toxic but less effective first-line regimen with mitoxantrone is of clinical benefit. Methods: A retrospective analysis of all pts with HRPC who received both D and M in either sequence in the Province of British Columbia to evaluate toxicity and clinical efficacy in terms of median overall survival (OS), progression free survival (PFS) and PSA decline of ≥ 50%. Results: 83 pts were identified from the provincial pharmacy formulary database, 68 had charts available for review: 35 pts received D followed by M (D-M) and 33 pts received M followed by D (M-D). Both groups were well balanced for prognostic factors (Gleason score, time from diagnosis, ECOG performance status, PSA, hemoglobin, alkaline phosphatase, LDH, PSA doubling time, extend of disease). Patients who received D-M had a trend towards longer OS (22 months (m), 95% CI: 17.2 - 26.8) compared to patients treated with M-D (15m, 95% CI: 10.4 - 19.6, p = 0.12). Median number of 2nd line chemotherapy cycles was 3 and PFS was 2–3m in both groups. 2nd line D produced a higher PSA response (44%) compared to M (15%, p = 0.012) but this did not translate into a survival benefit: OS for patients treated with 2nd line D and M was 7m (95%CI: 3.7 - 10.3) and 12m (95% CI: 7.8 - 16.2, p = 0.27). 2nd line chemotherapy was associated with a high frequency of adverse events: 64% of patients treated with D and 46% patients who received M required dose reduction, delay or stop of chemotherapy due to toxicity. On univariate analysis, LDH was prognostic for survival but there were no apparent predictive factors for response to 2nd line therapy. Conclusions: Our results favor docetaxel given up-front for patients with HRPC. 2nd line chemotherapy with either D or M is of limited efficacy and tolerability. Patients should be enrolled into clinical trials when being considered for 2nd line chemotherapy. No significant financial relationships to disclose.