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Abstract 1053: A patient-derived xenograft model demonstarates the effectiveness of combined oxaliplatin and 5-fluorouracil for advanced small bowel adenocarcinoma

Background: Combination oxaliplatin and capecitabine therapy is recommended to treat advanced small bowel adenocarcinoma (SBA). However, SBA is rare, and limited preclinical studies and randomized clinical trials have been conducted. Methods: A patient-derived xenograft (PDX) was established from an advanced SBA patient with liver metastasis and peritoneal metastasis. Growth inhibition by oxaliplatin, irinotecan, 5-fluorouracil (5-FU), and 5-FU in combination with oxaliplatin, irinotecan, or paclitaxel was assessed using the PDX. Drug sensitivity against oxaliplatin, irinotecan, 5-FU, and paclitaxel was assessed using SBA cells from the PDX. The patient’s clinicopathological and genetic features were compared with the PDX to evaluate it as a preclinical model. Results: 5-FU, but not oxaliplatin and irinotecan showed statistically significant growth inhibition compared to control group ( P = 0.0024). Among the combination treatment with 5-FU, oxaliplatin showed the highest tumor growth inhibition rate of 0.84 or 1.1, which was 0.46 for irinotecan and 0.49 for paclitaxel, respectively. IC 50 of SBA cells was significantly lower against oxaliplatin and higher against paclitaxel compared with colon cancer cell line HT29. These results corresponded to the clinical response to FOLFOX (folinic acid+5-FU+oxaliplatin) and FOLFIRI (folinic acid+5-FU+irinotecan). PDX pathological and genetic features resembled those of the patient. Conclusions: We established a preclinical model comprising the PDX from SBA and SBA cells from the PDX. This model showed that the combination of oxaliplatin and 5-FU was a reasonable standard therapy for advanced SBA. A preclinical model comprising PDX and tumor cells from PDX seems to be useful for rare tumors including SBA. Citation Format: Tomoki Yamano, Jihyung Song, Kei Kimura, Akihito Babaya, Michiko Hamanaka, Kozo Kataoka, Naohito Beppu, Masafumi Noda, Masataka Ikeda, Naohiro Tomita. A patient-derived xenograft model demonstarates the effectiveness of combined oxaliplatin and 5-fluorouracil for advanced small bowel adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1053.