The Observation Of The Efficacy And Adverse Reaction Of The Combination Chemotherapy Of Irinotecan Plus Folinic Acid/continuous5-fluorouracil Bimonthly FOLFIRI Regimen In Treating Advanced Colorectal Adenocarcinoma

Background and purpose：Colorectal carcinoma(CRC) is a major causeof cancer-related mortality. In the1990s, several first-line phase Ⅲtrailsshowed a significant improvement in result with the addition ofCPT-11(irinotecan, which is a specific inhibitor of topoisomerase Ⅰ) toFu-LV combination therapy(FOLFIRI).We observed the efficacy andadverse reaction of the combination chemotherapy of irinotecan plusfolinic acid/continuous5-fluorouracil bimonthly FOLFIRI regimen intreating advanced colorectal adenocarcinoma and investigated thecorrelation of UGT1A1*28and UGT1A1*6gene polymorphisms withirinotecan－associated adverse events and efficacy in the patients withmetastatic colorectal cancer (mCRC) treated with irinotecan－basedchemotherapy.METHODS: Analysis of UGT1A1*28and UGT1A1*6genepolymorphisms was performed in26patients with histologically provedadvanced colorectal adenocarcinoma by amplifying the gene fragmentsusing PCR and direct sequencing．Then the26patients received at least2cycles of chemotherapy with irinotecan180mg/m~2and folinic acid400mg/m~2,5-FU400mg/m~2,days1,5-FU2400mg/m~2for46-48h.Treatmentwas repeated every two weeks.We observed and recorded the adverseevents and efficacy during chemotherapy，and the incidence of differentgenotypes was compared. RESULTS: The distribution of the genotypes in26gastrointestinalcancer patients was as follows: UGT1A1*28wild－type (WT)genotype TA6/6(19，73.1%)，heterozygous genotype TA6/7(7，26.9%)，and homozygous genotype TA7/7(0); UGT1A1*6WTgenotype G/G (23，88.5%)，heterozygous genotype G/A (4，11.5%)，and homozygous genotype A/A (0).All patients were assessable fortoxicity and evaluable for treatment response. There were no completeresponses (CR),4(15.4%) partial response (PR), and18(69.2%) stabledisease. Four patients experienced grade Ⅲ or grade Ⅳdiarrhea. Themost common hematological toxicity was neutropenia. Grade Ⅲandgrade Ⅳ neutropenia were observed in six patients. There was nocase offebrile neutropenia. In the26mCRC cases，the incidence of grade3and4delayed diarrhea in the patients carrying UGT1A1*28(6/7and7/7) washigher than that in the WT genotype (6/6)(5.3%vs42.9%，P＜0.05).No significant difference of chemotherapeutic effect was observedbetween different genotypes.CONCLUSION: Bimonthly irinotecan in combination with folinic acidand5-fluorouracil was efficient and active with acceptable toxicities. TheUGT1A1*28(TA6/7and TA7/7) genotypes increase the risk of grade3and4delayed diarrhea in mCRC patients treated with irinotecan－based chemotherapy．...