Delay in administration of CDDP until completion of AGM-1470 treatment enhances antimetastatic and antitumor effects.
The efficacy of cis-diammine dichloroplatinum (CDDP) therapy in combination with continuous administration of angiogenesis inhibitor o-(chloroacetyl-carbamoyl) fumagillol (AGM-1470) was evaluated experimentally using a transplantable rat osteosarcoma line previously established in our laboratory. AGM-1470 (2.5 mg/kg body weight/week) was administered by Alzet osmotic pumps for 2 weeks starting from 7 days after tumor inplantation and CDDP (1.25 mg/kg) was given on days 21 and 24. The number of lung metastatic nodules was counted and the wet weights of the primary tumors were measured 5 weeks after tumor inplantation. Values with administration of CDDP 3 days after discontinuation of AGM-1470 were significantly lower than when the two agents were coadministered (P < 0.05). This animal model should facilitate optimization of the timing of combination therapy.
Morishita
T
T
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Japan.
Miyauchi
Y
Y
Mii
Y
Y
Miura
S
S
Honoki
K
K
Aoki
M
M
Kido
A
A
Yoshimoto
M
M
Tamai
S
S
Tsutsumi
M
M
Konishi
Y
Y
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003510:Cyclohexanes; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D008297:Male; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012516:Osteosarcoma / Q000098:blood supply / Q000188:drug therapy / Q000556:secondary; D051381:Rats; D011916:Rats, Inbred F344; D012717:Sesquiterpenes / Q000008:administration & dosage
D003510:Cyclohexanes; D012717:Sesquiterpenes; D002945:Cisplatin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol