Improved therapeutic index of cisplatin analogue: B-85-0040 by circadian timing.
1. B-85-0040 is a new cisplatin analogue with dose limiting myelosuppression. 2. The maximum tolerated dose ranges between 300 and 525 mg/kg for single i.p. bolus injection in mice. 3. Its toxicity is circadian-stage dependent with optimal tolerance between 16 and 17 hours after lights on. 4. B-85-0040 is active in L1210 leukemia. Anti-tumor activity seems to be unrelated to the circadian stage of treatment. Optimal drug timing can therefore increase its therapeutic index.
von Roemeling
R
R
Med. Oncology Div., Albany Medical College, NY.
Portuese
E
E
Salzer
M
M
Solis
O
O
Bennett
J
J
Sothern
R
R
Hoffmann
D
D
Sedlacek
H
H
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002940:Circadian Rhythm; D002945:Cisplatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D007928:Lethal Dose 50; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008811:Mice, Inbred DBA
C066002:B 85-0040; D002945:Cisplatin