Docetaxel in advanced renal carcinoma. A phase II trial of the National Cancer Institute of Canada Clinical Trials Group.

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, RP56976) a semi-synthetic 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 > or = 2.0 x 10(9)/L, platelets > or = 100 x 10(9)/L) and biochemical (serum creatinine and bilirubin < or = 1.5 x normal, transaminases < or = 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.