This is the first study of selective drug delivery in humans using a novel PSA-activated agent. L-377202 was cleaved to produce detectable levels of the active metabolites Leu-Dox and Dox. L-377202 was well tolerated and established a safe dose level for further study.
This first study evaluated the efficacy and safety of imatinib in patients with early androgen sensitive prostate cancer following local therapy. As a single agent at this dosing, imatinib had limited biochemical activity.
This study demonstrated the activity of docetaxel alone, without androgen ablation, in patients with PSA progression after completion of local therapy. Treatment with docetaxel in this population with early disease progression was well tolerated, biochemically active, and was not androgen ablative. Accrual to national phase III studies in early disease is now critical and should be strongly encouraged to determine the ability of early chemotherapy to improve survival.
Recent studies of docetaxel have demonstrated improved survival over mitoxantrone and prednisone in patients with hormone-refractory prostate cancer (HRPC), supporting the study of novel docetaxel-containing regimens as primary therapy or following initial docetaxel-based therapy. To evaluate the combination of docetaxel and vinorelbine in the treatment of patients with HRPC, 40 patients with proven adenocarcinoma of the prostate with progressive metastatic disease despite androgen ablation were enrolled onto this phase II trial. Patients were treated with docetaxel 60 mg/m2 on day 1 and vinorelbine 15 mg/m2 on days 1 and 8 of a 21-day cycle. All patients received dexamethasone 8 mg twice daily for 4 days starting 1 day prior to the docetaxel infusion. After the first three patients were enrolled, filgrastim was added on days 2-6 and 9-13. Of the 40 patients enrolled, 19 had no prior chemotherapy and 21 had received at least one prior chemotherapy regimen. Of the 19 patients without prior chemotherapy and the 21 with prior chemotherapy, 7 (37%) and 6 (29%) , respectively, demonstrated a decrease in prostate specific antigen by > 50% maintained for at least 4 weeks. Out of eight patients with measurable disease, one achieved a partial response and four demonstrated stable disease. There was one patient with deep vein thrombosis, and febrile neutropenia was noted in only three patients after the protocol was modified to include filgrastim support. The combination of docetaxel and vinorelbine with filgrastim was well tolerated and active against HRPC in patients with or without prior chemotherapy.
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