Purpose: To determine the maximum-tolerated dose (MTD) of cyclosporine (CsA) infusion administered with etoposide for 3 days in patients with cancer.

Patients and Methods: Of the 72 registered patients, 26 were treated initially with CsA and etoposide. Forty-six received etoposide alone until disease progression, and 31 of these proceeded to CsA and etoposide. CsA was administered as a 2-hour loading dose (LD) and as a 3-day continuous infusion (CI); doses were escalated from 2 to 8 mg/kg LD and 5 to 24 mg/kg/d CI.

Results: Fifty-seven patients were treated with 113 cycles of CsA with etoposide. Steady-state serum CsA levels (nonspecific immunoassay) more than 2,000 ng/mL were achieved in 91% of the cycles at CsA doses a 5 mg/kg LD and a 15 mg/kg/d CI. The major dose-related toxicity of CsA was reversible hyperbilirubinemia, which occurred in 78% of the courses with CsA levels greater than 2,000 ng/mL. Myelosuppression and nausea were more severe with CsA and etoposide. Other CsA toxicities included hypomagnesemia, 60%; hypertension, 29%; and headache, 21%. Nephrotoxicity was mild in 12% and severe in 2% of the cycles. Tumor regressions occurred in