Metastatic castrate-resistant prostate tumors typically overexpress receptors for vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), two of the key cell-surface targets for sunitinib, an oral drug that has emerged as a first-line treatment for renal cell carcinoma. It was reasonable to think that sunitinib, with its dual binding to PDGF and VEGF, would improve upon that, Dr. Zurita said.
Preliminary data from an ongoing phase I/II multicenter study of sunitinib in combination with docetaxel and prednisone, the first to evaluate this new drug in the prostate cancer setting, suggest that this is the case, at least for some patients. During the lead-in period, sunitinib showed a curious trivalent effect on PSA levels. Seven patients had a mean PSA decline of 40%, with three of them showing a greater than 50% decrease. In contrast, 12 patients showed a steep mean rise in PSA of 273% followed by a drop during the 2-week rest period. Six others showed steady mean increases of 73% that did not drop back down during the rest period.
The combination of docetaxel and sunitinib produced PSA reductions of greater than 50% below baseline levels in 10 of the 25 patients (40%). Four of the 20 patients (20%) with measurable disease at baseline had a partial tumor response, based on RECIST criteria, and 11 (55%) had stable disease. Five patients progressed during the year-long follow-up period.
Based on the phase I results, the researchers determined that docetaxel 75 mg/m2 plus sunitinib 37.5 mg represented the optimal dose levels for the ongoing phase II portion of the trial. Sunitinib was generally well tolerated at this dose, and did not significantly add to the side-effect burden of docetaxel plus prednisone. The data was presented in 2007, ECCO abstract 4025.
This trial is now continued as a Phase II study. It is “of unproven value” and should be considered experimental – Phase 1/2 Safety and Pharmacokinetic Study of SU011248 In Combination With Docetaxel (Taxotere®) and Prednisone in Patients With Metastatic Hormone Refractory Prostate Cancer (HRPC). The goal of this Phase I portion of this clinical research study is to find the highest dose of the drug sunitinib malate (Sutent®, SU011248) that can be given safely with docetaxel (Taxotere®) and prednisone to patients with prostate cancer whose cancer has spread to other organs. It is “of unproven value” and should be considered experimental.O. Guérin et al, Supra-additive antitumor effect of sunitinib malate (SU11248, Sutent®) combined with docetaxel. A new therapeutic perspective in hormone refractory prostate cancer Journal of Cancer Research and Clinical Oncology Issue Volume 134, Number 1 / January, 2008 Pages 51-57
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