The semisynthetic podophyllotoxin derivative VP-16-213 (NSC 141540) has been evaluated in a phase II study in patients with small cell anaplastic carcinoma of the lung. The drug was administered as an oral solution, the drinking ampoule, in doses of 100 mg twice a day for 4 days in 30 patients previously treated with intensive combination chemotherapy and for 5 days in 10 untreated patients. The courses were repeated every third week with dose modifications according to individual tolerance. All patients had measurable disease and objective responses were obtained in 20 patients (50%), 15 previously treated (50%) and 5 untreated patients (50%). The median time for response after the start of treatment was 15 days (range 6-42) and the median duration of response was 56 days (range 16-147). Dose-limiting toxicity was principally hematologic, consisting of leukopenia, but gastrointestinal toxicity and alopecia were also observed. The study demonstrated that VP-16-213 administered as an oral solution is highly effective against small cell anaplastic carcinoma of the lung without clinical cross-resistance to CCNU, cyclophosphamide, methotrexate, or vincristine.