Calcium folinate

Patients in control group were treated with FOLFOXIRI. On the 1st day, 150–180 mg/m² irinotecan (approval no. NMPN H20084572; Qilu Pharmaceutical Hainan Co., Ltd., Shandong, China) was intravenously injected for 90 min, and 200 mg/m² calcium folinate (approval no. NMPN H20000584; Jiangsu Hengrui Medicine Co., Ltd., Jiangsu, China) was also intravenously injected for 2 h; then 400 mg/m² 5-fluorouracil (approval no. NMPN H31020593; Shanghai Xudong Haipu Pharmaceutical Co., Ltd., Shanghai, China) was intravenously injected, and then 2,400 mg/m² 5-fluorouracil was pumped into peripheral vein for 46 h. Patients in observation, based on the treatment in control group, received intravenous drip of 5 mg/kg bevacizumab (approval no. registration certificate no. S20120068; Roche Diagnostics, Indianapolis, IN, USA) for ≥1.5 h in the first, and for ≤1 h in the second time. Two groups of patients received the above treatment once every two weeks. After treatment, the curative effects on patients were dynamically evaluated, and the surgical resection could be scheduled when it was resectable. This study was approved by the Ethics Committee of The Second Affiliated Hospital of Zhengzhou University. Signed written informed consents were obtained from the patients and/or guardians.

Animals in the treated groups received 5-FU injections (40 mg/kg) (Shangdong Qilu Pharmaceutical Co., Ltd., China) in 0.2 mL 0.9% sodium chloride intraperitoneally once a day for 5 consecutive days starting on day 0. No medicine was given during the last two days of the week[18 (link)]. In addition, calcium folinate (Jiangsu Hengrui Medicine Co., Ltd., China) was injected (45 mg/kg) intraperitoneally twice a day; the first injection was given one hour before the 5-FU injection, and the second injection was given at the same time as the 5-FU injection. This procedure was repeated for three weeks. Animals in the control group received intraperitoneal injections of 0.1 mL sterile water at the same time points as the treated animals received 5-FU injections.

The control group (43 patients) received classical FOLFOX chemotherapy, which consisted of oxaliplatin (Zhejiang Hisun Pharmaceutical Co., Ltd.; approval number: GYZZ H20093487) administered intravenously at a dose of 135 mg/m² for 2 h on day 1, calcium folinate (Jiangsu Hengrui Medicine Co., Ltd.; approval number: GYZZ H20000418) administered at 200 mg/m² for 2 h on days 1-3, and 5-fluorouracil (Hainan Zhuotai Pharmaceutical Co., Ltd.; approval number: GYZZ H20051626) given continuously by an intravenous pump at a dose of 2600 mg/m² for 46-48 h, every 3 weeks for a total of 6 cycles of chemotherapy.
The observation group (39 patients) underwent the treatment of olaparib combined with bevacizumab. To wit, olaparib (AstraZeneca; registration certificate number: H20180049) was taken orally at a dose of 200 mg twice daily- once in the morning and once in the evening; bevacizumab injection (Shanghai Roche Pharmaceutical Co., Ltd.; approval No.: S20120068) was intravenously injected at 15 mg/kg for 0.5-1 h on day 1, every three weeks for a total of six cycles of chemotherapy.