Phase II study of vinorelbine in patients with androgen-independent prostate cancer

Purpose: To evaluate the efficacy and toxicity of vinorelbine in a phase II study in patients with progressive metastatic androgen-independent prostate cancer. Patients and methods: Forty-seven men with progressive metastatic prostate cancer refractory to first-line or second-line hormonal therapy were treated with vinorelbine, a semi-synthetic vinca-alkaloid. Vinorelbine was given, on an outpatient schedule, at 25 mg/m(2) weekly for at least eight weeks or until progression or excessive toxicity. Results: Forty-seven patients were included in the study, 33 being evaluable for tumour response, 36 for response to PSA, 21 for clinical benefit and 45 for toxicity. Median actual weekly dose was 19 mg/m(2) (range 12.0-26.2 mg/m(2)). Six of thirty-six patients (17%) demonstrated a biologic response with a 50% or more decline in serum PSA on two consecutive measurements taken at least two weeks apart. The median duration of biologic response was 2.7 months. Two of three patients with measurable disease obtained an objective response but remained unconfirmed. No change disease was reported in 23 patients (49%). On entry into the study, 30 patients had symptomatic bone pain and required narcotic or non-narcotic analgesics. Clinical benefit from vinorelbine was achieved in 15 patients out of 21 (32% of the intent to treat analysis population and 71% of the assessable patients). Due to the low number of questionnaires (QLQ-C30) filled in, it was insufficient to allow any statistical analysis. The median survival was 10.2 months. Toxicity was mainly haematologic with 51% of patients experiencing grade 3 or 4 granulocytopenia. Three patients developed deep vein thrombosis. Non-haematologic toxicity, mainly nausea and neurotoxicity, was mild. Conclusion: The administration of weekly vinorelbine appears to be a safe treatment for those patients with androgen-independent prostate cancer and poor prognosis features who require chemotherapy. These results provide data for future investigation of vinorelbine in combination regimens.