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SCHEDULE DEPENDENCY OF THE ANTILEUKEMIC ACTIVITY OF THE PODOPHYLLOTOXIN‐DERIVATIVE VP 16–213 (NSC‐141540) IN L1210 LEUKEMIA
Author(s) -
Dombernowsky Per,
Nissen Nis I.
Publication year - 1973
Publication title -
acta pathologica microbiologica scandinavica section a pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0365-4184
DOI - 10.1111/j.1699-0463.1973.tb03564.x
Subject(s) - podophyllotoxin , medicine , toxicity , pharmacology , zoology , biology , chemistry , stereochemistry
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.