Phase II study of daily oral etoposide in refractory germ cell tumors.

Etoposide was found to be schedule-dependent in both preclinical and clinical trials. A study was initiated in March 1988 at Indiana University (Indianapolis, IN), using daily oral etoposide in patients with refractory germ cell tumors. The dose was 50 mg/m2/d, administered daily until progression or toxicity not ameliorated by dose adjustment occurred. Twenty-two patients have been entered to date. Primary sites were testis (11 patients), retroperitoneum (five patients), and mediastinum (six patients). All 22 patients had had previous treatment with cisplatin/etoposide combination regimens, including six patients who were also previously treated with high-dose etoposide and carboplatin with autologous bone marrow transplantation. The median number of treatment regimens was 2.9 (range, 1 to 4). Five patients had progressive disease during treatment with etoposide. Median length of treatment was 11.5 weeks (range, 2 to 30), with six patients continuing on treatment. Median white blood cell nadir was 1.5 x 10(9)/L, median hemoglobin nadir 9.1 g/dL, and the median platelet nadir 184,000/microL. Granulocytopenia required temporary cessation of treatment in eight patients and dose reductions in four. Five patients developed granulocytopenic fevers, including pneumonia (two patients) and bacteremia (one patient). Additionally, two patients (who tested negative for human immunodeficiency virus) died from Pneumocystis pneumonia with granulocyte counts higher than 500/microL. Of 21 evaluable patients (there was one protocol violation), three responded with a greater than 90% decrease in markers and a greater than 50% decrease in measurable radiographic disease. One of these had previously progressed on cisplatin/etoposide combination therapy. Three other patients responded with a greater than 90% decrease in markers but with stable radiographic disease; two of them had previously resected teratoma. The remaining ten patients were nonresponders. In conclusion, daily oral etoposide has definite activity in refractory germ cell tumors. Further evaluation of this regimen is warranted.