Response to second-line chemotherapy in patients with hormone refractory prostate cancer receiving two sequences of mitoxantrone and taxanes

Objectives. Clinical trials have demonstrated a survival benefit with docetaxel chemotherapy, but limited data exist regarding the activity of second-line chemotherapy. Methods. We retrospectively identified all patients at one institution who received at least two chemotherapy regimens for hormone-refractory prostate cancer, one mitoxantrone-based and the other taxane-based, either including docetaxel or paclitaxel. Patients were evaluated using criteria modified from the Prostate-Specific Antigen Working Group. Results. A total of 68 patients were analyzed; 33 patients received mitoxantrone followed by taxane-based treatment, and 35 received taxane-based chemotherapy followed by mitoxantrone. The median patient age was 66 and 58 years and the median prostate-specific antigen at the start of treatment was 23 and 24 ng/mL in the mitoxantrone-first and taxane-first group, respectively. The response rates to taxane-based chemotherapy were greater whether it was used first or second (P < 0.0001). Progression-free survival (PFS) was longer with taxanes than with mitoxantrone, whether used first or second (P < 0.05). However, the corresponding total PFS from start of the first regimen to progression during the second regimen was similar at 39.9 and 38.7 weeks (P = 0.67). Overall survival was also not significantly different (15.2 and 17.1 months, P = 0.97). Neither age nor the interval from diagnosis to chemotherapy influenced the differences in PFS. Conclusions. Taxane-based chemotherapy is active before or after mitoxantrone. Although PFS was longer with taxane-based chemotherapy, the total PFS and overall survival were equivalent for both sequences in this retrospective analysis, suggesting that taxane-based chemotherapy retains activity, even if delayed. Although responses were seen with mitoxantrone after taxanes, the median PFS was short, and new agents are needed after taxane-based chemotherapy.