Daily oral etoposide in the treatment of cancer

Etoposide is one of the few cancer chemotherapy agents that is schedule-dependent in both preclinical and clinical studies. A randomized trial of etoposide as initial therapy in extensive small cell lung cancer (SCLC) demonstrated the superiority of a 5-day course versus the same total dose administered over 24 hours. The recent availability of oral etoposide capsules has led to further exploration of etoposide's schedule-dependency through the use of daily oral etoposide. Initially, studies at Indiana University and the Hoosier Oncology Group concentrated on refractory germ cell tumors and refractory SCLC. Although both of these tumor types are sensitive to etoposide combination chemotherapy as initial treatment, it is rare to see a response with any single agent in refractory disease. In 25 patients with refractory germ cell tumors, we observed 5 objective responses (20%). In addition, 3 other patients (12%) clearly achieved antitumor effect with a greater than 90% reduction in tumor markers, although radiographic findings remained stable. In refractory SCLC, 1 complete and 5 partial responses were observed in 26 patients, for a 23% response rate. Twenty-five of the 26 had received prior cisplatin/etoposide and 14 also had received prior cyclophosphamide/doxorubicin/vincristine. Daily oral etoposide is capable of producing palliation and objective responses in heavily pretreated patients and may be a preferable method of administration. Future trials are planned using daily oral etoposide as a component of combination chemotherapy as first- and second-line therapy in patients with SCLC.