Second-line chemotherapy and its evaluation in small cell lung cancer.

The literature on second-line chemotherapy for small cell lung cancer between 1989-1999 is reviewed. The reports consisted mainly of phase II studies and included a total of 1749 patients. The information was frequently incomplete with respect to duration of response on first-line chemotherapy and the length of treatment free interval. The overall second-line response rate was 20%. Obviously, new chemotherapy regimens are needed for relapsed small cell lung cancer. We propose a methodology for future trials based on the distinction between sensitive and refractory patients. The latter group of patients who progress on or within a short time of induction of treatment are candidates for single arm phase II trials with agents with unknown or new mechanisms of action or new combination regimens. The sole endpoint of this type of phase II studies is response rate. For sensitive patients we propose re-induction chemotherapy as the standard against which investigational agents or combination regimens should be tested. Major end-points include response rate, toxicity and quality of life. Regimens with demonstrated therapeutic activity in this setting could be tested as first-line chemotherapy in phase II trials.