Safety signal mining of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity / 中国药房

OBJECTIVE To mine the safety signals of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity， and to provide reference for the selection of clinical rational treatment plan and the prevention and treatment of drug adverse reaction （ADR）. METHODS Reporting odds ratio method and proportion report ratio method were used to analyze adverse drug event （ADE） reports of FOLFOX scheme and FOLFIRI scheme in FDA adverse event reporting system during January 1， 2004-June 30， 2022. The potential safety signals of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity were mined. RESULTS The amounts of ADE reports related to FOLFOX scheme and FOLFIRI scheme were respectively 3 454 and 1 359； the proportions of male and female patients involved were 1.50∶1 and 1.67∶1 in these two schemes， respectively. The top five countries with the largest number of reports were the United States， Japan， France， Italy and the United Kingdom， respectively accounting for 58.48% and 53.79% of the total reported cases. More than 90% of patients took no more than 5 drugs in combination， the proportion of patients receiving FOLFOX scheme and FOLFIRI scheme combined with anti-angiogenic drugs or epidermal growth factor receptor inhibitors was 45.45% and 86.82%， respectively. Totally 443 ADE reports of FOLFOX scheme-induced hepatotoxicity were collected， and 22 ADR signals were generated， including hepatic sinusoidal obstruction syndrome， nodular regenerative hyperplasia， drug-induced liver injury， blood bilirubin increased， etc. Totally 128 ADE reports of FOLFIRI scheme- induced hepatotoxicity were reported， and 9 ADR signals were generated， including blood bilirubin increased， hepatotoxicity， steatohepatitis， hepatic steatosis， etc. CONCLUSIONS FOLFOX scheme and FOLFIRI scheme can cause different types of hepatotoxicity. Clinical drug monitoring should be strengthened to guarantee drug safety.

Efficacy and safety of second-line chemotherapy with EOX and FOLFIRI in advanced gastric cancer / 西安交通大学学报(医学版)

Objective To study the clinical efficacy and safety of the regimen of oxaliplatin plus epirubicin and capecitabine (EOX)as the second-line treatment for advanced gastric cancer.Methods We randomly divided 107 patients with advanced gastric cancer for treatment between January 1,2010 and June 1,2013 in our hospital after DCF chemotherapy failed into EOX group (n=56)and FOLFIRI group (n=51).We observed the response rate (RR),disease control rate (DCR),time to progression (PFS),overall survival (OS)and adverse reactions in the two groups.Results RR in EXO group and FOLFIRI group was 28.57% and 25.49%,respectively,without significant difference (P＞0.05).DCR in EXO group and FOLFIRI group was 73.21% and 66.67%,without significant difference (P＞0.05).The median progression-free time (mPFS)in EOX group and FOLFIRI group was 7.4 months and 8.1 months (χ2=0.547,P=0.460),and the median overall survival (mOS)was 19.3 months and 18.5 months (χ2=1.886,P=0.170).The mainly side effects associated with the regimen were leukopenia, thrombocytopenia, anemia, nausea/vomiting, hand-foot syndrome, stomatitis, and peripheral neurotoxicity. Neutropenia,thrombocytopenia,anemia,and diarrhea in EOX group were more frequent than those in FOLFIRI group (P＜0.05).Conclusion The regimen based on EOX is effective in patients with advanced gastric cancer after DCF chemotherapy failed and the toxicities are tolerable.

Efficacy and Safety of FOLFIRI after Failure of FOLFOX-4 in Advanced Gastric Cancer / 대한소화기학회지

BACKGROUND/AIMS: The purpose of this study was to investigate the efficacy and safety of irinotecan based FOLFIRI chemotherapy as a second-line treatment after failure of FOLFOX-4 chemotherapy in patients with advanced gastric cancer. METHODS: Fifty-two patients who were pathologically diagnosed with unresectable gastric cancer and received FOLFIRI chemotherapy after failure of FOLFOX-4 chemotherapy between September 2005 and February 2012 were enrolled in this study. Data were collected by retrospectively reviewing the medical records. The response to chemotherapy was assessed every 3 cycles by World Health Organization criteria and long term survival was analyzed. The toxicities were evaluated for every course of chemotherapy according to National Cancer Institution (NCI) toxicity criteria version 3.0. RESULTS: Median age of the patients was 57 years. Median overall survival (OS) and time to progression (TTP) were 7.8 and 5 months, respectively. The number of patients showing complete remission, partial remission, stable disease, and progressive disease were 0 (0.0%), 9 (17.3%), 30 (57.7%), and 13 (25.0%), respectively. The overall response rate was 17.3%. During a total of 345 cycles, anemia worse than NCI toxicity grade 3 occurred in 2.9%, leukopenia in 20.3%, neutropenia in 12.2%, and thrombocytopenia in 1.5%. Patients with less organ involvement by metastasis, less than 34 U/mL of CA 19-9 and good responsiveness to third cycle of second line chemotherapy were associated with longer OS and TTP. CONCLUSIONS: FOLFIRI chemotherapy has a modest efficacy with acceptable toxicities in patients with advanced gastric cancer as a second-line treatment. Further well-controlled studies are needed to elucidate the efficacy of FOLFIRI chemotherapy as second-line treatment in patients with advanced stomach cancer.

Clinical research of bevacizumab plus different kinds of chemotherapieutics for metastatic colorectal cancer / 中国药学杂志

OBJECTIVE: To compare the efficacy and safety of bevacizumab plus FOLFIRI program or FOLFOX program for metastatic colorectal cancer.

Modified FOLFIRI as Second-Line Chemotherapy after Failure of Modified FOLFOX-4 in Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m2 in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 as a bolus followed by 600 mg/m2 as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.

Modified FOLFIRI as Second-Line Chemotherapy after Failure of Modified FOLFOX-4 in Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m2 in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 as a bolus followed by 600 mg/m2 as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.

Retrospective Analysis of Patients Treated with Cetuximab plus FOLFIRI for Previous Irinotecan-combined Chemotherapy in Metastatic Colorectal Cancer

PURPOSE: Many reports about efficacy of cetuximab in the prolongation of survival have been published. Especially, the combination of cetuximab and FOLFIRI has a high activity even in prior irinotecan refractory metastatic colorectal cancer (mCRC). Beside small number of patients, we are trying to evaluate the efficacy and safety of cetuximab combined with FOLFIRI for patients who prior irinotecan chemotherapy had failed. METHODS: A retrospective analysis of 26 patients treated with cetuximab with FOLFIRI from July 2006 to August 2007 was done. All patients had already been treated with FOLFIRI chemotherapy in 1st line or 2nd line regimens for mCRC. The initial dose of cetuximab was 400 mg/m2 at the 1st week, after which the dose was 250 mg/m2 weekly plus FOLFIRI biweekly. We defined 1 cycle as 8 weeks, and the responses were evaluated at week 8. RESULTS: The median follow-up period was 6.2 (1.1~13.9) months. After 8 weeks, 50% of the patients had a partial response, and the disease control rate was 57.5%. The median time to progression was 3 months. EGFR expression and tumor response had no correlation (P=0.07). Skin reaction and tumor response (median time to progression) had a significant correlation (P= 0.022). Cetuximab did not increase the toxicity associated with FOLFIRI, except for an acneiform rash. CONCLUSIONS: Cetuximab combined with FOLFIRI chemotherapy was effective in treating mCRC patients after FOLFIRI regimen chemotherapy.