Randomized dose-response evaluation of etoposide in small cell carcinoma of the lung: a Southeastern Cancer Study...

To evaluate postulated dose-response relationships of etoposide (VP-16) for patients with recurrent small cell carcinoma of the lung, a prospectively randomized study was undertaken. VP-16 was administered iv at three dose levels: 300, 600, and 900 mg/m2. Based on historical information, a 20% response rate was anticipated in the standard-dose level and the study was designed to be able to detect a response rate of 40% in either of the high-dose levels. The planned number of patients required in each arm was 45, with an alpha-level of 0.1 and a beta-level of 0.2. The total number of patients actually entered was less than the planned number due to a low response rate. Seventy-seven of 79 treated patients were eligible, and 26, 27, and 26 patients were treated at each dose level, respectively. Toxicity was predominantly hematologic, with the higher dose levels substantially more toxic. Response to therapy was infrequent, with only four partial responses achieved and distributed between all dose levels. In this study, using previously treated patients, VP-16 at standard-dose or at moderate-dose increments had minimal activity.