Potentiation of docetaxel antitumor activity by batimastat against mouse forestomach carcinoma.
OBJECTIVE
To improve the treatment of tumors, we studied the combined effects of docetaxel and batimastat (BB-94) on mouse forestomach carcinoma (MFC), and compared them with doxorubicin.


RESULTS
In vitro, growth curve analysis, MTT assay and clonogenic assay used to determine the cytotoxic effect of docetaxel or/and BB-94 on MFC cell showed that docetaxel but not BB-94 had a significant cytotoxicity, and the effect of docetaxel wasn't enhanced by BB-94. In early stage MFC tumor model, obvious antitumor effect of docetaxel or doxorubicin given i.v. at maximum tolerated dose (MTD, docetaxel: 20 mg/kg; doxorubicin: 6 mg/kg) every 4 days for 3 injections (q4d x 3), even that of BB-94 (30 mg/kg i. p. qd x 20) was observed. Tumor growth inhibition was greater for docetaxel-batimastat (96.0%) than for doxorubicin-batimastat (88.0%), docetaxel (89.0%), doxorubicin (68.0%) and BB-94 (33.0%), and the effect of docetaxel could be potentiated by BB-94. Docetaxel also showed activity against advanced stage MFC tumor in dose-dependent manner, and was more effective at MTD than doxorubicin with 4/5 regressions, 46.5 days tumor growth delay and 2.8log(10) tumor cell kill.


CONCLUSIONS
Our results suggest that in the MFC model with dose and schedule used, docetaxel is an effective cytotoxic new drug against MFC tumor and BB-94 enchances the antitumor activity of docetaxel.
Gu
B
B
Department of Clinical Pharmacology, North Taiping Road Hospital, Beijing 100039.
Wu
D
D
Lü
H
H
Li
M
M
Gao
H
H
Wan
Y
Y
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000077143:Docetaxel; D004357:Drug Synergism; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000473:pathology*; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D043823:Taxoids; D013876:Thiophenes; D000077143:Docetaxel; D010649:Phenylalanine; C080985:batimastat