Combined chemotherapy and differentiation therapy in the treatment of advanced non-small-cell lung cancer

Background: In this phase-II pilot study a cisplatin-based treatment was combined with biological agents capable of inducing differentiation in non-small-cell lung cancel (NSCLC) cells with the aim of ameliorating response to chemotherapy. Patients and methods: Forty patients (PTS) with inoperable stage III-B or IV NSCLC were treated with cisplatin (CDDP) 24 mg/m(2) on days 1 to 5, 5-fluorouracil (5-FU) 500 mg/m(2) by continuous infusion on days 1 to 5 and vindesine (VDS) 3 mg/m(2) on days 1 and 5. Beta-interferon (beta-IFN) 1 x 10(6) IU/m(2) subcutaneously 3 times a week and retinyl palmitate (R) 50,000 IU orally BID were administered between chemotherapy cycles. Responders were maintained with the same dose of beta-IFN plus R 15,000 IU BID. Half of the PTS had an ECOG performance status of 0-1, 62% of tumours were of squamous histology and 77.5% of PTS had stage IV disease. A median of four courses of chemotherapy per PT was delivered. Results: Forty PTS were evaluable. Seventeen PTS responded (RR 42%, 95% C.I. 27%-57%). Of the 17 responders 13 had squamous histology. The median response duration was 5.1 months. The median overall survival was 9.1 months. Gastrointestinal toxicity occurred in 58% of PTS, anaemia in 20%, leukopenia in 30%. Conclusions: The association of CDDP, VDS, 5-FU, beta-IFN and R shows activity in NSCLC, particularly in tumours with squamous histology, with a substantial toxicity.