High-dose etoposide (VP-16) in small-cell lung cancer

Etoposide (VP-16) is one of the most active drugs against small-cell lung cancer. There may be a steep dose-response relationship, and we have explored the use of etoposide as a single agent in a high dose (1,200 mg/m²) without bone marrow transplantation, for patients with very bulky, extensive-stage disease. This therapy is well tolerated in patients having good performance status, with myelosuppression representing the major toxicity. Our data suggest there may truly be a steep dose-response relationship. We have continued to explore intensive induction therapy for selected very poor-prognosis patients by adding high-dose cyclophosphamide (100 mg/kg) to high-dose etoposide. This combination is also very myelotoxic, but quite similar to etoposide alone. Our current study adds cisplatin (120 mg/m²) to the high-dose cyclophosphamide-etoposide schedule in an attempt to take advantage of the synergism seen with these drugs in various other circumstances. This series of studies will give us information regarding the feasibility of intensive induction therapy and provide data for the design of phase III studies.