Among new patients with small cell lung cancer (SCLC), 20% to 25% are over 70 years of age and account for 8,000 cases annually in the United States. For such patients, intensive, aggressive, cytotoxic, combination chemotherapy is not often used because of its association with unacceptable morbidity and mortality rates. However, treatment of these patients is often indicated, if not demanded. Etoposide is among the most active agents for the treatment of SCLC; both oral (PO) and intravenous preparations are available. The bioavailability of etoposide PO ranges from 15% to 75%. We carried out a phase II trial of etoposide PO in elderly patients (greater than or equal to 70 years of age) with a confirmed histologic diagnosis of SCLC. Patients were treated with etoposide capsules 800 mg/m2, with the total dose divided over 5 consecutive days. Cycles were repeated every 3 to 4 weeks for a total of six cycles. All treatment was administered on an outpatient basis. Staging procedures were confined to physical examination, chest x-ray, and laboratory investigations. Further staging procedures were carried out only if clinically indicated. In September 1985, 53 patients (35 male, 18 female) with a median age of 73 years (range, 70 to 95) were treated. After staging, 24 patients (45%) had limited disease (LD); the remaining 29 patients had extensive disease (ED). Overall response was 79% (complete response [CR], 17%; partial response, 62%). CRs were seen in 8 of 24 patients (33%) with LD and in 1 of 29 patients (3%) with ED. Median survival of all patients was 9.5 months (range, 1 to 22+) with 20 patients still alive; the toxicity rate was acceptable. Total alopecia developed in all patients, whereas significant neutropenia (8%) and thrombocytopenia (6%) were rare. There were no treatment-related deaths or hospital admissions. In this study, we showed activity of etoposide PO in patients with SCLC; these results were comparable with those reported for more intensive combination regimens. For elderly patients, etoposide PO provides excellent palliative treatment, with a high response rate and significant prolongation of survival. In addition, therapy is associated with minimal toxicity and can be administered entirely on an outpatient basis.(ABSTRACT TRUNCATED AT 400 WORDS)