Increased therapeutic efficacy of intra-arterial carboquone chemotherapy on a limb tumor in rats, by using an acidic vehicle adjusted with lactate.
We previously reported that the cytotoxicity of carboquone (CQ) was potentiated in vitro and in vivo under acidic conditions. In this study, an acidic vehicle adjusted with lactate at various low pHs was used for CQ intra-arterial (i.a.) injection, in order to enhance the antitumor effects of i.a. CQ chemotherapy. Treatments were evaluated in Wistar/KA rats bearing a limb tumor 5 days after the inoculation of 3 x 10(6) syngeneic RBT-1 tumor cells into the hind limb. In chemotherapy experiments using an intrafemoral injection of CQ at 1.5 mg/kg in phosphate-buffered saline (PBS, pH 7.4) or in an acidic vehicle at pH 5.0 or 6.0, the antitumor effects seen in rats given CQ in acidic vehicles, evaluated by tumor weight 14 days after treatment, were significantly greater than that seen in rats given CQ in PBS. There were no significant differences either in changes of body weight or in the number of leukocytes after treatment between the groups given CQ in PBS and in an acidic vehicle at pH 6.0. Although in the group given CQ at 2.0 mg/kg in PBS, the antitumor effect was the same as that observed in rats given CQ at 1.5 mg/kg in an acidic vehicle at pH 6.0, the side effects observed in the former group were much severer than in the latter group. These data suggest that the antitumor effect of i.a. CQ chemotherapy can be potentiated by using an acidic vehicle.
Hasuda
K
K
Department of Experimental Cell Research, Kyusyu University, Fukuoka, Japan.
Kobayashi
H
H
Taniguchi
S
S
Baba
T
T
D000818:Animals; D001835:Body Weight; D002021:Buffers; D002225:Carbazilquinone / Q000008:administration & dosage* / Q000494:pharmacology; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000473:pathology; D005121:Extremities / Q000473:pathology*; D005260:Female; D006863:Hydrogen-Ion Concentration; D007261:Infusions, Intra-Arterial; D007773:Lactates / Q000494:pharmacology*; D019344:Lactic Acid; D007958:Leukocyte Count / Q000187:drug effects; D009368:Neoplasm Transplantation; D014677:Pharmaceutical Vehicles; D010710:Phosphates; D051381:Rats; D012965:Sodium Chloride; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology
D002021:Buffers; D007773:Lactates; D014677:Pharmaceutical Vehicles; D010710:Phosphates; D002225:Carbazilquinone; D019344:Lactic Acid; D012965:Sodium Chloride