Sunitinib in combination with docetaxel and prednisone in patients (pts) with metastatic hormone-refractory prostate cancer (mHRPC)

Abstract

5166 Background: Overexpression of VEGF and PDGF has been implicated in prostate cancer progression and bone metastases. Sunitinib is an oral, multitargeted inhibitor of VEGFRs, PDGFRs, and other tyrosine kinases which may improve the efficacy of chemotherapy in pts with mHRPC. We performed a multicenter phase I/II study of sunitinib in combination with docetaxel and prednisone as first-line therapy in pts with mHRPC. The combination dose was established in phase I (Zurita et al, ECCO. 2007). Final results from phase II will be reported. Methods: Pts received treatment in a 21-day cycle: sunitinib 37.5 mg/d on days 1–14, docetaxel 75 mg/m2 on day 1, and prednisone 5 mg BID on days 1–21. Dose reductions were permitted for treatment-related toxicity. The primary endpoint was PSA response rate (PSA Working Group Criteria). Secondary endpoints included tumor response rate (RECIST), safety and patient-reported outcomes. Results: Fifty-five pts were enrolled and 13 remained on study at the time of the data cutoff (1 Oct 08). Thirty-six discontinued from the study due to disease progression (16), adverse events (AEs; 13), consent withdrawal (6) and other (1). Six pts completed the study (16 cycles) and continued treatment on another protocol. Pts received a median of 23 weeks of therapy (range, 2–84). The most common treatment-related grade 3–4 AEs were neutropenia (75%), febrile neutropenia (15%), fatigue (15%), stomatitis (7%), and anorexia (7%). Sunitinib dose reduction to 25 mg/d was required in 14 pts (26%), and 3 pts (6%) had a further dose reduction to 12.5 mg/d. Docetaxel dose reduction to 60 mg/m2 was required in 18 pts (33%). PSA responses occurred in 31 pts (56%), with a preliminary median time to PSA progression of 42.1 weeks. Out of 33 pts with measurable disease, thirteen (39%) had a confirmed partial response (PR) and another 7 (21%) had an initial PR. The median progression-free and overall survivals have not been reached, but the probability of survival at 48 weeks is 92.4% (95% CI: 77.5, 97.6). Patient-reported assessments of pain and quality of life will be reported. Conclusions: Sunitinib in combination with docetaxel and prednisone is tolerated and has antitumor activity in pts with mHRPC, as indicated by both PSA and RECIST-defined tumor responses. [Table: see text]