Oral VP-16-213 in advanced bronchogenic carcinoma and toxic effects when combined with methotrexate

Forty-six patients with histologically confirmed lung cancer received treatment with the cytotoxic drug VP-16-213 in a dose of 100 mg twice daily, given orally for five days. The overall objective response rate was 11 out of 46 (24%) or 11 of the 33 (33%) who survived to receive two cycles. The drug was effective in all histological types. Only one patient developed leucopenia. This demonstration of the safety of VP-16-213 and its effectiveness suggested that this drug might be used in combination chemotherapy. A series of pilot studies showed unexplained marrow toxicity when VP-16-123 combined with vincristine was given with either methotrexate of adriamycin.