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Teniposide, VM-26 (Vumon), was administered in a dose of 60 mg/m2 on days 1 to 5 every third week to 36 patients with histologically confirmed small-cell lung cancer. None had previously received chemotherapy or radiotherapy. The median age was 73 years (range, 52 to 79). Thirty-three patients were evaluable; 21 of these had local disease. Five patients had bone marrow metastases, four had liver involvement, and one CNS metastases. All patients had a performance status less than or equal to 2 before the start of treatment. Thirty patients obtained a response (90%), ten of whom had a complete remission (30%). The median duration of remission was 8+ months (range, 1.1 to 17+ months), whereas the median survival was 8.7 months (range, 1.9 to 20 months). Toxicity was primarily hematologic, with leukopenia the only dose-limiting effect. Besides alopecia, all other side effects were minimal including nausea and vomiting. We find these results provocative in regard to the response rate and the duration of response obtained as well as in reference to the dismal results that prior investigations in previously treated patients have shown. These data may indicate the need for reconsideration of the usual strategy for performing phase II trials.

The epipodophyllotoxin derivatives VM 26 and VP 16-213 are currently entering phase III studies. The mechanism of their action is incompletely understood, but the greatest lethal effect is experienced in the late S and G2 phases. In transplanted tumors both drugs have shown marked schedule dependency and human studies also support this. As a single agent VP 16-213 is among the most active drugs in small-cell carcinoma of the lung. Significant clinical activity (> 20% response frequency) has been observed for both drugs in Hodgkin's disease, non-Hodgkin lymphomas and possibly in other more rare tumors (monocytic leukemia, hepatoma and teratoma). Although further clinical studies of both drugs would be ideal, it seems possible at present to justify a discontinuation of VM-26 in order to concentrate the efforts on VP 16-213. Further studies are needed to define optimal dose and schedule and place in combination chemotherapy.

Fifty-one patients with small cell bronchogenic carcinoma received 60 mg/m2 of teniposide iv on Days 1-5 every 3 weeks. All patients had received previous combination chemotherapy. Twenty patients with prior etoposide treatment and 20 without such prior treatment were evaluable. A partial response was observed in one of 20 and in five of 20 patients, respectively. The duration of responses was short (28-50 days). Sixty-one percent of patients experienced grade 3 or 4 toxicity on the World Health Organization scale. The activity in previously treated patients not exposed to etoposide was considerable, justifying further evaluation of teniposide in the treatment of small cell carcinoma of the lung.