Interferon-alpha and 13-cis-retinoic acid as maintenance therapy after high-dose combination chemotherapy with growth factor support for small cell lung cancer - a feasibility study

This randomized phase II multi-center study was designed to determine the t ime to progression, duration of response and the feasibility of an intensif ied maintenance regime consisting of a combination of interferon (IFN)-alph a and retinoic acid after high-dose combination chemotherapy and radiothera py in patients with small cell lung cancer. The patients received four cour ses of combination chemotherapy consisting of ifosfamide, carboplatin and e toposide, with higher doses of ifosfamide and carboplatin given in the firs t course, with routine growth factor support. Responding patients were then randomly assigned to one of three maintenance therapy arms. All patients w ith limited disease (LD) were given thoracic radiotherapy before maintenanc e therapy and those who had also achieved a complete response (CR) or minim al residual disease (MRD) received prophylactic cranial irradiation. In Arm 1 patients received IFN-alpha-2a, 6 MIU s.c. TIW for 4 weeks, followed by 3 MIU s.c. TIW, and 13-cis-retinoic acid 1 mg/kg/day p.o. BID daily. In Arm 2 patients received trophosphamide 100-150 mg/day p.o. BID. No maintenance treatment was given in Arm 3, the control group. Maintenance therapy was c ontinued for 1 year. Eighty-five patients were treated according to the pro tocol. Twenty-one patients achieved CR, four achieved MRD and forty-two ach ieved partial responses to chemotherapy and radiotherapy. Sixty patients (7 1%) were randomly assigned for maintenance treatment. Median survival was 1 7.1 months in the IFN-alpha-retinoic acid arm, 12.4 months in the trophosph amide arm and 13.5 months in the control arm. One-year survival rates were 82, 56 and 55%, respectively. Duration of response was 6.5, 5.5 and 4.7 mon ths, respectively. Time to progression was 8.6, 8.0 and 6.8 months, respect ively The differences were not statistically significant. The IFN-gamma-ret inoic acid maintenance treatment was well tolerated. Patients who received IFN-alpha-retinoid maintenance therapy lived longer after the onset of prog ressive disease. The treatment regime was effective, feasible and well tole rated. [(C) 2000 Lippincott Williams & Wilkins.].