DOCETAXEL IN ADVANCED RENAL-CARCINOMA

Background: Most patients diagnosed with renal carcinoma developed metastatic disease at some time during their course, with available therapy inducing response in only a small proportion of patients. Docetaxel (Taxotere(R), RP56976) a semisynthetic analogue of paclitaxel with a broad range of in vitro antitumor activity, was evaluated in a phase II study. Methods: Eligibility criteria included histologically proven metastatic or advanced, bidimensionally measurable disease, no prior chemotherapy, immunotherapy, or hormonal therapy, adequate hematologic (neutrophils greater-than-or-equal-to 2.0 x 10(9)/L, platelets greater-than-or-equal-to 100 x 10(9)/L) and biochemical (serum creatinine and bilirubin less-than-or-equal-to 1.5 x normal, transaminases less-than-or-equal-to 3 x normal) parameters, WHO performance status of at least 2, and a life expectancy of > 12 weeks. Docetaxel was administered in a dose of 100 mg/m2 as a 1 hour intravenous infusion every 3 weeks. The first 2 patients entered onto the study were not premedicated for hypersensitivity reactions; subsequent patients received dexamethasone 10 mg and diphenhydramine 50 mg i.v. 30 minutes prior to docetaxel. Results: Twenty patients were entered onto the study, with 2 considered inevaluable for response. Sixty cycles of therapy were administered, with only 2 cycles delivered at a dose of 55 mg/m2 or less. No objective responses were seen; 1 patient demonstrated a mixed response. Neutropenia was significant, with 42/60 cycles developing grade 3/4 granulocytopenia. Fifty-five percent of patients demonstrated hypersensitivity reactions despite the premedication regimen employed, higher than that of the phase I studies which established the dose and schedule used in this trial. Conclusions: 1) Docetaxel is an ineffective agent in advanced renal carcinoma. 2) The high rate of hypersensitivity reactions suggests the need for more intensive premedication and/or slower infusion times at this dose level.