Sequence-dependent antitumor effect of VP-16 and 1-beta-D-arabinofuranosylcytosine in L1210 ascites tumor.
The sequence-dependence of the antitumor effect of etoposide (VP-16) and 1-beta-D-arabinofuranosylcytosine (ara-C) was investigated against the L1210 ascites tumor in BDF1 mice. Treatment with VP16 (7.5 or 15 mg/kg) and ara-C (25 or 500 mg/kg) was administered intraperitoneally on days 1, 4 and 7 after tumor inoculation. Six hour pretreatment with 15 mg/kg VP16 followed by 500 mg/kg ara-C yielded a 100% cure rate, but only a 20% cure rate was obtained with the reverse sequence. Simultaneous administration of 15 mg/kg of VP-16 and 500 mg/kg ara-C interacted synergistically, producing a 70% cure rate. In contrast with the results obtained with VP-16 and 500 mg/kg ara-C, simultaneous administration of 25 mg/kg ara-C neither antagonized nor potentiated the antitumor effect of VP-16. Twenty-five mg/kg ara-C was too low to produce any antitumor effect with VP-16 in simultaneous administration. At every dose investigated, pretreatment with VP-16 followed by ara-C was the most effective antitumor schedule in L1210 leukemia. This sequence of drug administration did not cause greater toxicity as measured by weight loss or toxic death.
Ohkubo
T
T
Department of Pediatrics, Mie University, School of Medicine, Japan.
Higashigawa
M
M
Kawasaki
H
H
Kamiya
H
H
Sakurai
M
M
Kagawa
Y
Y
Kakito
E
E
Sumida
K
K
Ooi
K
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D007939:Leukemia L1210 / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D003561:Cytarabine; D005047:Etoposide