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

ABSTRACT

BACKGROUND: Docetaxel and mitoxantrone are considered first-line chemotherapeutic options in patients with hormone-refractory prostate cancer (HRPC), but their clinical effectiveness in a second-line setting is unknown. Therefore, the authors conducted a population-based retrospective study to establish activity and tolerability of second-line docetaxel or mitoxantrone in HRPC. METHODS: The study included 68 patients who had failed androgen ablation therapy and who received docetaxel and mitoxantrone in either sequence. Clinical efficacy in terms of median overall survival (OS), progression-free survival (PFS), posttreatment prostate-specific antigen (PSA) decline of > or = 50% and treatment-related toxicity were evaluated. RESULTS: Of 68 patients, 35 received docetaxel followed by mitoxantrone, and 33 received mitoxantrone followed by docetaxel. Both groups were comparable for recognized pretreatment prognostic factors. Patients who received docetaxel first-line had a trend toward longer median OS compared with patients treated with second-line docetaxel after mitoxantrone failure (22 mos, 95% confidence interval [CI], 17.2-26.8 mos vs. 15 mos, 95% CI, 10.4-19.6 mos). Median number of second-line chemotherapy cycles was 3 and median PFS survival was 2-3 months in both groups. Second-line docetaxel produced a higher PSA response compared with mitoxantrone (38% vs. 12%, P = 0.012), but this did not translate to a survival benefit. Both second-line docetaxel and mitoxantrone were associated with a high frequency of treatment-related adverse events that resulted in dose reduction, delay, or discontinuation (64% and 46% of patients, respectively). CONCLUSIONS: Study results favored docetaxel given up-front for patients with HRPC considered suitable for further chemotherapy. Second-line docetaxel or mitoxantrone had limited efficacy and tolerability. Patients who are candidates for second-line chemotherapy, should be enrolled into clinical trials.