Schedule Dependency of the Antileukemic Activity of the Podophyllotoxin‐derivative Vp 16–213 (Nsc‐141540) in L1210 Leukemia

The schedule dependency of the antileukemic activity and toxicity of the podophyllotoxin derivative VP 16–213 (NSC‐141540) was investigated against the L1210 ascites tumour in N/D mice. In the toxicity experiments LD10 for intraperitoneal (i.p.) treatment on day 1 only, once daily for five days and once daily day 1, 5, 9 and 13 was found to be 47.0, 7.7 and 33.6 mg/kg, respectively. In the therapy experiments treatment was started 24 hours after inoculation of 105 L1210 cells i.p. The optimal concentrations gave for treatment on day 1 only 75 per cent increase in lifespan and 13 per cent cures. Daily treatment for 5 days was superior to treatment day 1 only, this was again exceeded by treatment at 2–4 days intervals. Even better results were obtained with treatment at 4 days intervals (cure rate 63 per cent), while treatment at 6–8 days intervals gave inferior results. Divided treatment every 3 hours for 24 hours demonstrated a significant superiority over a single treatment. This together with the mechanism of action could indicate, that VP 16–213 is a cell cycle specific drug.