Current status of etoposide in the management of small cell lung cancer

Etoposide is a schedule‐dependent drug with excellent activity against small cell lung cancer (SCLC). Single‐agent etoposide achieves overall response rates ranging from 15% to 84%, depending on the schedule of drug administration and the characteristics of the treated population. The route of etoposide administration (intravenous versus oral) has little impact on response rate, provided appropriate dose adjustments are made for oral therapy. In combination with other active agents, etoposide has proven particularly effective in the management of SCLC. Etoposide can be substituted for doxorubicin or vincristine in the cyclophosphamide, doxorubicin, and vincristine (CAV) regimen without loss of efficacy. The etoposide and cisplastin (EP) combination is thought to be synergistic and has proven to be an effective salvage regimen for CAV failures. A regimen that alternates CAV and EP has been found by some investigators to be modestly more effective against SCLC than CAV alone; however, EP alone may be as useful as an alternating regimen. Most studies to date have demonstrated that EP induction is at least as effective as any other standard induction regimen. However, EP has the potential advantage of being more easily integrated with thoracic radiation therapy (RT). This is particularly important in limited‐disease patients: two recent pilot studies employing EP induction with hyperfractionated thoracic RT yielded 2‐year survival rates of greater than 50%. These promising results are being evaluated further in an ongoing Phase III trial in the United States. The available data indicate that etoposide is one of the most active agents against SCLC and therefore should be included as a component of induction therapy in all patients. New schedules of etoposide administration warrant further study.