Results of a phase III, double-blind, placebo-controlled trial of megestrol acetate modulation of P-glycoprotein-mediated drug resistance in the first-line management of small-cell lung carcinoma.

The objective of this study was to determine if the addition of megestrol acetate (MA), a modulator of P-glycoprotein-mediated drug resistance, to first-line cytotoxic therapy in patients with limited and advanced stage small-cell lung cancer (SCLC) would improve median time to disease progression and median overall survival. Secondary outcomes evaluated were response rates and patient symptom profile. Between 1992 and 1995, 130 eligible patients were randomized in a double-blind fashion to receive standard first-line therapy consisting of alternating courses of cyclophosphamide/doxorubicin/vincristine and etoposide/cisplatin (and thoracic radiotherapy for limited stage patients), along with either placebo or MA 160 mg t.i.d. for 8 days commencing 3 days before initiation of each cycle of chemotherapy. Treatment was continued for a maximum of six cycles. A total of 130 eligible patients were randomized, 65 to each arm. Fifty-two per cent of patients had limited disease and 48% had advanced disease. The median time to disease progression in limited stage disease was 46 weeks in the placebo arm and 43 weeks in the MA arm (P = 0.71) and in advanced stage disease was 28 weeks in the placebo arm and 27 weeks in the MA arm (P = 0.92). The median overall survival in limited stage disease was 75 weeks in the placebo arm and 75 weeks in the MA arm (P = 0.56) and in advanced stage disease was 41 weeks in the placebo arm and 39 weeks in the MA arm (P = 0.96). There was no consistent statistical difference in response rates or patient symptom profiles between the two treatment arms. The addition of MA, in the dose and schedule used, to standard first-line cytotoxic therapy in SCLC did not result in a significant improvement in response rates, symptom profile, median time to disease progression or overall survival.