Influence of the stage of advancement of leukemia L1210 in mice on the optimal schedule of treatment of cytosine arabinoside (NSC-63878).
Treatment with cytosine arabinoside given intraperitoneally (ip) every 3 hours for 24 hours on every fourth day (Q3h/24h/4d) from 1 day after ip implantation of 10(6) or 10(7) leukemia L1210 cells in mice, was not observed to be superior to the same treatment after implantation of 10(5) cells. Similarly, when cytosine arabinoside therapy was delayed until Day 5 after 10(5) tumor cells were implanted, treatment Q3h/24h/4d did not provide a therapeutic advantage over treatment with a single injection every second or fourth day. A single treatment of the advanced disease with cyclophosphamide did not restore the sensitivity of the disease to the Q3h/24h/4d treatment schedule. Whether treatment with cytosine arabinoside was started on Days 1, 3, or 5, the optimal total dose per day for treatment given once every fourth day was 12-20 times greater than the optimal total dose per day for treatment given in eight equal injections every fourth day. Via the oral route, the Q3h/24h/4d treatment regimen was not superior to one treatment every fourth day from Day 1. The data clearly show that when the initial inoculum is high (10(6) or 10(7) cells) or when the disease is advanced, the response to cytosine arabinoside therapy does not display treatment-schedule dependency for the Q3h/24h/4d schedule.
Kline
I
I
Microbiological Associates, Inc, Bethesda, MD, USA.
Woodman
R J
RJ
Gang
M
M
Sirica
A
A
Venditti
J M
JM
Goldin
A
A
D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage*; D018450:Disease Progression; D004334:Drug Administration Schedule; D007274:Injections, Intraperitoneal; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D003520:Cyclophosphamide