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Doxorubicin/vinblastine combined with the P-glycoprotein inhibitors trifluoperazine and verapamil was evaluated in the treatment of patients with metastatic renal carcinoma. Patients were treated with starting doses of doxorubicin/vinblastine of 30 mg/m(2) (doxorubicin) and 3 mg/m(2) (vinblastine) intravenously every 2 weeks, combined with 4 days of oral trifluoperazine/verapamil at 2 mg tid (trifluoperazine) and 160 mg tid (verapamil) administered I day before the chemotherapy was initiated. Response was assessed every three cycles of treatment. Of 26 evaluable patients, there were no responders. Six patients had stable disease for greater than 6 months on treatment. Therapy was generally well tolerated but 7 of 26 patients developed grade 4 granulocytopenia, including one patient who died due to sepsis. The possible reasons for the failure of P-glycoprotein inhibitors to enhance the effect of chemotherapy are discussed. |
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