Synergistic antitumor activity of vincristine and VP-16-213

The potential interaction of the antitumor agents vincristine and VP-16-213 was investigated in vivo. DBA/2 mice were inoculated with 10(6) P388 murine leukemia cells, after which single IP injections of saline only, vincristine only, VP-16-213 only, or a combination of vincristine and VP-16-213 were administered. Long-term survival (greater than 60 days) was observed in 0/45, 1/45 (2%), 9/135 (7%), and 44/135 (33%) mice, respectively (P less than 0.001). Treatment was most effective when VP-16-213 was administered 0-72 h after vincristine. A similar trend was observed in mice bearing P1534 murine leukemia. These data demonstrate synergistic antitumor activity between vincristine and VP-16-213 in a murine model.