PURPOSE: There is no standard therapy for progressive or recurrent small cell lung cancer (SCLC). Lomustine, etoposide and cyclophosphamide oral chemotherapy were evaluated in a feasibility study of efficacy survival and toxicity. PATIENTS AND METHODS: 71 patients were included in this study, 36 in second-line and 35 in third-line chemotherapy. They received lomustine (CCNU) 80 or 120mg on D1 only, etoposide 100mg from D1 until D6 up to D14 and cyclophosphamide 100mg from D1 until D6 up to D14 every 4 weeks. The dosages of CCNU and duration of administration of the other two drugs were adapted to an original therapeutic risk level table on D1 and throughout treatment. Evaluation based on clinical status, response and weekly blood counts was performed before each cycle until progression. RESULTS: 70 patients were evaluable. They received between 1 and 20 cycles of treatment (mean=3.7 for second-line and 3.0 for third-line treatment). Complete responses were observed for 3 patients in each line, and partial responses were noted in 13 patients in second-line and 8 patients in third-line, resulting in a total response rate of 27/70=38%. Median-survival time estimated from the start of second- or third-line treatment was the same in the two subgroups: 4.4 months, but the patients in two subgroups presented different clinical characteristics. Haematological toxicity was severe with three toxic deaths as frequently observed in this setting, but hospitalisations were uncommon during this fully oral treatment that provided a very good quality of life for these out-patients. Consumption of health care resources for this low-cost and ambulatory treatment was limited. CONCLUSION: The similar efficacy with acceptable safety, the ease of administration in out-patients and the economical advantages justify comparison of this oral chemotherapy with conventional intravenous chemotherapy. A randomised phase II trial is on-going in France for second-line SCLC patients on this theme.