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.