Antitumor activity of bevacizumab in human gastric cancer xenografts.

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Objective: Bevacizumab (BV), a humanized antibody to VEGF, has been reported to show clinical benefit in the patients with CRC, BC, and NSCLC. Bevacizumab is also expected for showing efficacy in gastric cancers, then we examined the antitumor activity of BV on human gastric cancer xenograft models as a single agent or in combination with chemotherapies.
 Methods: Five gastric cancer cell lines of various histological types were inoculated into nude mice, and treated with 1-25 mg/kg of BV or human IgG once a week for 3 weeks. Capecitabine (CAPE,239 mg/kg/day, orally, daily for 14 days, and 7 day’s rest) or cisplatin (CDDP,5 mg/kg, intravenously, once a week for 3 weeks)were administered in combination with BV in a GXF-97 model. Tumor growth inhibition rate (TGI%) was determined after 3 weeks treatment.
 Results: BV showed antitumor activity in tubular adenocarcinoma GXF-97 and MKN-28, mucinous adenocarcinoma SC-08-JCK, and solid type of poorly differentiated adenocarcinoma 4-1ST and MKN-45. TGI% of BV at 5 mg/kg of BV were 62%,56%,75%,68%, and 73%, respectively. Combination of BV with CAPE and CDDP in the GXF-97 model showed significantly more potent antitumor activity than CAPE + CDDP or BV alone. (BV: 78%, CAPE: 63%, CDDP: 73%, CAPE + CDDP: 106%, BV + CAPE + CDDP: 122%).
 Conclusion: Bevacizumab as a single agent showed antitumor activity in various histological types of gastric cancers, and more potent antitumor activity in the combination with capecitabine and cisplatin. Evaluation of the efficacy and safety of bevacizumab in clinical gastric cancers would be warranted.