ABSTRACT
INTRODUCTION: Recombinant human interferon-a2b (rHuIFN-alpha2b) and Interleukin-2 have limited effectiveness in the treatment of metastatic renal cell carcinoma (MRCC). Gemcitabine (Gemzar) is also reported to have activity against MRCC, and recent in vitro, in nude mice xenografts, and human data suggests increased activity of gemcitabine (Gemzar) when combined with IFN-alpha2b. PURPOSE: A phase I clinical trial utilizing gemcitabine (Gemzar and rHuIFN-alpha2b was conducted in patients with metastatic renal cell carcinoma. METHODS: Treatment consisted of: gemcitabine (Gemzar) 600 mg/m2 I.V. weekly and rHuIFN-alpha2b 1.0 MU/m2 (dose level A) or 3.0MU/m2 S.C. (dose level B) three times a week for 6 weeks with a 2 weeks rest period. RESULTS: Thirteen patients were entered into the trial and were evaluated. Dose limiting toxicity was predominantly hematologic, and was seen at dose level B. This included grade 3 anemia (1 patient), neutropenia (1 patient), and nausea (1 patient) and grade 4 neutropenia (1 patient). The maximal tolerated dose was gemcitabine (Gemzar) 600 mg/m2 I.V. weekly and rHuIFN-alpha2b 1.0 MU/m2 three times a week. CONCLUSION: This combination of gemcitabine (Gemzar) and rHuIFN-alpha2b has significant hematologic toxicity despite low doses of each agent. Further investigation of this combination using this schedule is not recommended.
