Clinical efficacy and adverse reactions of SBRT combined with mFOLFOXIRI and cetuximab in liver metastases after colorectal cancer surgery / 国际肿瘤学杂志

Objective:To investigate the efficacy of stereotactic body radiotherapy (SBRT) combined with modified FOLFOXIRI (mFOLFOXIRI, irinotecan, oxaliplatin, leucovorin and fluorouracil) and cetuximab in the treatment of postoperative liver metastases in patients with KRAS, BRAF and NRAS gene wild-type colorectal cancer, and to evaluate treatment-related adverse reactions.Methods:A total of 86 patients with postoperative liver metastases from colorectal cancer diagnosed in Shandong Daizhuang Hospital from January 2018 to January 2021 were selected, all of whom were KRAS, BRAF and NRAS gene wild-type. All patients were divided into control group and study group according to the random number table method, with 43 cases in each group. The patients in the control group were treated with mFOLFOXIRI and cetuximab, 14 days a cycle, for a total of 12 cycles. The patients in the study group were treated with SBRT for liver metastases on the basis of the control group. Two patients in the control group were withdrawn from the study due to intolerance of myelosuppression (grade 4), and patients in the study group were withdrawn from the study due to intolerance of 1 case of myelosuppression, 1 case of gastrointestinal reaction and 1 case of abnormal liver function (all grade 4). The efficacy, median progression-free survival (PFS), median overall survival (OS) and adverse reactions were compared between the two groups after treatment.Results:After 12 cycles of treatment, the objective response rate (ORR) and disease control rate (DCR) of the study group were 55.00% (22/40) and 80.00% (32/40) respectively, which were higher than 31.71% (13/41) and 58.54% (24/41) of the control group, with statistically significant differences ( χ2=4.48, P=0.034; χ2=4.37, P=0.037). After treatment, 14 patients (35.00%) in the study group were resectable, which was higher than 6 patients (14.63%) in the control group, with a statistically significant difference ( χ2=4.52, P=0.034). The median PFS and median OS of the study group were 9.2 months and 19.5 months respectively, which were longer than 6.5 months and 15.2 months of the control group, with statistically significant differences ( χ2=8.83, P=0.015; χ2=7.52, P=0.027). There were no significant differences in incidences of leukopenia [55.00% (22/40) vs. 46.34% (19/41), χ2=0.61, P=0.436], anemia [45.00% (18/40) vs. 39.02% (16/41), χ2=0.30, P=0.585], thrombocytopenia [37.50% (15/40) vs. 31.71% (13/41), χ2=0.30, P=0.584], nausea and vomiting [55.00% (22/40) vs. 48.78% (20/41), χ2=0.31, P=0.575], constipation and diarrhea [20.00% (8/40) vs. 17.07% (7/41), χ2=0.12, P=0.734], liver function damage [35.00% (14/40) vs. 29.27% (12/41), χ2=0.31, P=0.581], peripheral sensory neuropathy [30.00% (12/40) vs. 26.83% (11/41) ), χ2=0.10, P=0.752], acute cholinergic syndrome [12.50% (5/40) vs. 14.63% (6/41), χ2=0.08, P=0.779] and fatigue [52.50% (21/40) vs. 43.90% (18/41), χ2=0.60, P=0.439]. Conclusion:SBRT combined with mFOLFOXIRI and cetuximab is more effective than drug therapy alone in patients with liver metastases after colorectal cancer surgery, which can effectively prolong the survival period, and the adverse reactions are tolerable.

Chinese expert consensus on the clinical application of the Chinese modified triplet combination with irinotecan, oxaliplatin and continuous infusional 5-fluorouracil/leucovorin for colorectal cancer / 中华胃肠外科杂志

Colorectal cancer is the second most common malignant tumor in China. The FOLFOXIRI regimen, which combines 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan, is a high-intensity and highly effective chemotherapy regimen. However, the original regimen is poorly tolerated in Chinese patients. In order to promote the standardized and rational application of FOLFOXIRI regimen by clinicians in China, "

Safety and efficacy of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) in Chinese patients with advanced colorectal cancer / 中华肿瘤杂志

Objective@#To establish the maximum tolerated dose (MTD) of 5-fluorouracil, leucovorin, oxaliplatin and irinotecan (FOLFOXIRI), and to evaluate the safety and efficacy in Chinese patients with advanced colorectal cancer.@*Methods@#Patients were treated with a regimen consisting of infusional 5-fluorouracil (2 400 mg/m2 on day 1), leucovorin (200 mg/m2 on day 1), oxaliplatin (85 mg/m2 on day 1), and irinotecan (at doses from 150 to 180 mg/m2 on day 8) according to the dose-escalation schema. Treatment was repeated every 14 days. The UDP-glucuronosyl transferase (UGT) 1A1 genotypes were analyzed in the patients with dose-limiting toxicity (DLT).@*Results@#A total of 12 patients with advanced colorectal cancer were included. The MTD of FOLFOXIRI in these patients was oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, 5-fluorouracil 2 400 mg/m2 day 1, and irinotecan 150 mg/m2 day 8 every 2 weeks. The most common toxicities were nausea, diarrhea, leukopenia, neutropenia and fatigue. The DLTs were febrile neutropenia and diarrhea. The objective response rate was 66.7%.@*Conclusions@#Our results indicate that FOLFOXIRI regimen is considered safe and effective in Chinese patients with advanced colorectal cancer, and the MTD of FOLFOXIRI regimen for Chinese patients with advanced colorectal cancer is recommended.

Evaluation of efficacy and safety of modified infusion of fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) in treatment of metastatic colorectal cancer: A retrospective study of 21 cases / 解放军医学杂志

Objective To evaluate the safety and preliminary efficacy of mFOLFOXIRI (the combination of irinotecan, oxaliplatin and 5-fluorouracil with reducing dosages) in first-line treatment for Chinese patients with unresectable metastatic colorectal cancer (mCRC). Methods A total of 21 patients received mFOLFOXIRI treatment: irinotecan 150mg/m2 on day 1, oxaliplatin 85mg/m2 on day 1, leucovorin 200mg/m2 on day 1, and 5-fluorouracil (5-FU) 2800mg/m2 in a 48-h continuous infusion starting on day 1. The regimen was repeated every 2 weeks. Result All the 21 patients were evaluated for efficacy of the aforesaid therapeutic regimen, and the incidence of toxic effects. No death occurred in association with the treatment. The total rate of grade 3 to 4 adverse events was 42.9% (9/21) including 38.1% (8 cases) with grade 3 neutropenia and 4.8% (1 case) suffering from grade 3 anemia. One of 21 patients (4.8%) showed grade 4 neutropenia accompanied by fever. The delivered relative dose intensity of irinotecan, oxaliplatin and 5-FU during the entire treatment course were 93.4%, 98.5% and 97.6%, respectively of planned dosage. In the intention-to-treat analysis for treatment activity, 14 patients showed remission, 6 stability, and 1 with progression of the disease. The overall response rate was 66.7%, and the disease control rate was 95.2%. Three patients (15.8%) with residual liver metastases were radically resected after mFOLFOXIRI chemotherapy. Conclusions This mFOLFOXIRI project has manageable toxicity and is well tolerated in Chinese patients. The safety profile appears to be improved compared with standard FOLFOXIRI regimen. In addition, the antitumor activity and preliminary efficacy seem to be maintained.