Cisplatin-fotemustine combination in inoperable non-small cell lung cancer: preliminary report of a French multicentre phase II trial.

Fotemustine is a new nitrosourea derivative whose activity has been demonstrated on metastatic melanoma with specific activity on brain metastases and also on poor prognosis lung cancers. Results of in vitro studies of a cisplatin-fotemustine combination seem promising. In order to evaluate the efficacy and safety of this combination, we performed two trials. 6 patients entered a preliminary study whose schedule was cisplatin 120 mg/m2 on day 1 and fotemustine 100 mg/m2 on days 1 and 8. 22 patients were enrolled in a second study which added 120 mg/m2 cisplatin on day 22 followed by a 4-week rest period. In both trials, maintenance therapy consisted of cisplatin 100 mg/m2 and fotemustine 100 mg/m2 every 3 weeks until progression. Despite the poor prognostic factors which characterised our population (metastatic disease 86%, brain metastases 59%, < or = 80% performance status 45%), the results remain attractive with a 23% partial response rate (29% in non-pretreated patients). Moreover, 3 out of 8 patients with evaluable cerebral metastases achieved a partial response (37.5%). Toxicity was mild and related to the cumulative dose of cisplatin (peripheral neuropathy and renal toxicity). We concluded that these results need to be confirmed in a randomised trial.