Clinical study of the new podophyllotoxin derivative, 4'-demethylepipodophyllotoxin 9-(4,6-o-ethylidene- beta-D-glucopyranoside) (NSC-141540; VP-16-213), in solid tumors.

The new semisynthetic epipodophyllotoxin, 4'-demethylepipodophyllotoxin 9-(4,6-o-ethylidene- beta-D-glucopyranoside) (NSC-141540), was tested for antitumor activity against solid tumors and for clinical toxicity in 30 patients. The first two courses were given intravenously (60 mg/m2/day times 5, every 21 days), and subsequent courses were given orally (60-120 mg/m2/day times 5, every 21 days). The drug was subjectively well tolerated but induced considerable leukothrombocytopenia and alopecia. It demonstrated significant activity in oat cell carcinoma of the lung (eight responses out of 11 patients) and ovarian cancer (-our responses out of six patients). NSC-141540 has valuable cytostatic activity against these two tumors and warrants further clinical trials, especially in combination chemotherapy.