Phase I/II study of taxane and estramustine with samarium in patients with hormone refractory prostate cancer

Abstract

4732 Background: Though metastatic prostate cancer (PCa) is a systemic disorder, bone disease predominates in its clinical management. Sm-153 lexidronam (Quadramet) is a bone seeking radioisotope. Though used for pain, preliminary data suggests that Quadramet may have direct anticancer activity. To evaluate the toxicity and efficacy of systemic therapy given in combination with Quadramet, we initiated a phase I/II study in patients with hormone refractory PCa. Methods: Patients with progressive disease were first treated with fixed doses of taxol/estramustine, and were then treated with Quadramet, in a dose escalation fashion. The first six patients received taxol 200 mg/m2 plus estramustine (280 mg TID, for 5 days) given q 3 wks X 3 cycles. Subsequent patients received taxol 90 mg/m2 plus estramustine (for 3 days) q wk X 6, given q 8 wks X 2 cycles. Quadramet was administered in dose escalating fashion, starting at 1.0 mCi/kg, increasing to MTD. In addition to measurement of response and toxicities, dosimetry was evaluated by performing serial body scans. Results: Eight of twelve patients (75%) enrolled in the phase I trial had partial responses. One patient who did not respond to the combination of taxol/estramustine, had a significant PSA response after Quadramet. Dose limiting toxicity, grade 3 leukopenia, was seen in 1 of 6 people treated at the 1.5 mCi/kg level, and MTD has not yet been determined. While myelosuppression was the most common adverse effect, it has been mild and self limiting. Detailed dosimetry estimates will be provided. Conclusions: The combination of taxol/estramustine followed by Quadramet is a well tolerated and effective regimen for hormone refractory PCa. Early anecdotal findings provide proof-of-principal results supporting the notion of the benefit of adding bone directed agents to systemic therapy. Myelosuppression with the combination is mild, manageable, and does not limit future therapeutic options. No significant financial relationships to disclose.