Combination treatment of CC531-lac-Z rat liver metastases by chemoembolization with pemetrexed disodium and gemcitabine

摘要: Purpose: The aim of this study was to evaluate the combination effect pemetrexed disodium (MTA; Alimta; LY 231514) and gemcitabine (GEM) administered by hepatic artery portal vein chemoembolization (HACE PVCE) in a colorectal cancer rat liver metastasis model. Materials methods: Proliferation studies on CC531-lac-Z colon cells were performed using MTT assay obtain optimal schedule two antineoplastic agents. To generate diffuse metastasis, 4×106 tumor implanted into male WAG/Rij rats. MTA (30 mg/kg, 60 mg/kg, 90 mg/kg) locoregionally (PVCE) compared with repeated systemic intravenous injection. GEM (50 mg/kg) also given (HACE) as well systemically. All routes administration examined alone combination. Efficacy treatment terms metastases burden determined at end experiment measuring β-galactosidase activity chemoluminescence assay. Results: Combination experiments vitro showed more than additive tumor cell reduction after sequential exposure preceding (observed/expected ratio [O/E] =0.73). Experiments reverse sequence (GEM→MTA) resulted only effects (O/E ratio =1.08). Simultaneous drug less (O/E ratios ≥1.25). In vivo, locoregional HACE significantly effective bolus (P=0.03). Portal immediately inoculation ineffective. Repeated yielded slight load that significant versus control medium high doses (60 mg/kg, P=0.009; 90 mg/kg, P=0.046) but not intraportal chemoembolization. (60 and or (60 mg/kg) 80% tumor growth inhibition; maximally additive. Conclusion: A regimen-dependent synergistic both drugs found vitro. animals, superior treatment. regimen (intravenous inhibition. results indicate can successfully be combined favor further evaluation patients.