Platelet-derived growth factor receptor inhibitor imatinib mesylate and docetaxel: A modular phase I trial in androgen-independent prostate cancer: Mathew P, Thall PF, Jones D, Perez C, Bucana C, Troncoso P, Kim SJ, Fidler IJ, Logothetis C., Department of

Purpose dy the platelet-derived growth factor receptor (PDGFR) inhibitor imatinib mesylate in androgen-independent prostate cancer (AIPC), alone and in combination with docetaxel, we designed a modular phase I trial. Our goals were to [1] evaluate the toxicity and maximum-tolerated dose of docetaxel with imatinib, and [2] evaluate the decline of prostate-specific antigen (PSA) induced by imatinib alone, and imatinib and docetaxel. ts and methods -eight men with AIPC and bone metastases were enrolled to receive imatinib 600 mg daily lead-in for 30 days, then imatinib 600 mg daily and one of six possible doses of docetaxel weekly for 4 weeks every 6 weeks. s the imatinib lead-in module, one dose-limiting toxicity (DLT) event was observed, while two (7%) of 28 had PSA decline (both <50%). With imatinib and docetaxel, cycle 1 DLT was found in three of 12 patients at docetaxel 30 mg/m2, in three of four patients at docetaxel 45 mg/m2, and in five of six patients at docetaxel 35 mg/m2. DLTs (n = 40 total events) were principally fatigue (35%) and nausea (20%). Eight (38%) of 21 had PSA decline greater than 50%, and six (29%) of 21 had PSA decline less than 50%. Serial PSA declines beyond 18 months were observed. PDGFR-expressing tumor declined on serial bone marrow biopsies with combination therapy alone. sion matinib 600 mg daily, the maximum-tolerated dose of docetaxel was determined to be 30 mg/m2 weekly for 4 weeks every 6 weeks. Long-term responses were observed. The role of imatinib in modulating outcomes to docetaxel in AIPC is being tested in a randomized phase II trial.