Rosenberg JE et al. (2007) Activity of second-line chemotherapy in docetaxel-refractory hormone-refractory prostate cancer patients: randomized phase 2 study of ixabepilone or mitoxantrone and prednisone. Cancer 110: 556–563

The de facto standard second-line chemotherapy regimen for patients with hormone-refractory prostate cancer (HRPC) is a combination of mitoxantrone and prednisone. Ixabepilone (Bristol–Myers Squibb, New York, NY) has shown good anti-tumor activity as a first-line chemotherapy agent. Rosenberg and colleagues' multicenter, prospective, randomized study compared these two regimens when used as second-line chemotherapy in patients with taxane-refractory HRPC.

The study enrolled 86 patients with confirmed metastatic prostate cancer who had failed a course of taxane-based chemotherapy. The patients who underwent treatment (n = 82) were randomly allocated to receive either intravenous ixabepilone 35 mg/m2 every 21 days or intravenous mitoxantrone 14 mg/m2 every 21 days plus oral prednisone 5 mg twice daily. The study end points were objective response, time to PSA progression and unacceptable toxicity.

All patients underwent a median of three treatment cycles. Both groups showed similar values for median survival from baseline (ixabepilone 10.4 months, mitoxantrone 9.8 months) and the percentage of patients with a PSA decrease of ≥50% (ixabepilone 17%, mitoxantrone 20%). A positive response to previous taxane-based therapy increased the chance of responding to either of the study treatments; low lactate dehydrogenase level and absence of visceral metastases at baseline were independent predictors of increased survival. The most common grade 3–4 toxicity was neutropenia, which occurred in 54% of the ixabepilone group and 63% of the mitoxantrone/prednisone group.

The authors conclude that both second-line chemotherapy regimens showed modest efficacy, and they state that research must continue into novel, effective first-line chemotherapy agents.