The epipodophyllotoxin derivatives VM-26 and VP-16-213, 1976-1979, a review.

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.