***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE In metastatic colorectal cancer , phase III studies have demonstrated the superiority of fluorouracil ( FU ) with leucovorin ( LV ) in combination with irinotecan or oxaliplatin over FU + LV alone . This phase III study investigated two sequences : folinic acid , FU , and irinotecan ( FOLFIRI ) followed by folinic acid , FU , and oxaliplatin ( FOLFOX6 ; arm A ) , and FOLFOX6 followed by FOLFIRI ( arm B ) . PATIENTS AND METHODS Previously untreated patients with assessable disease were r and omly assigned to receive a 2-hour infusion of l-LV 200 mg/m(2 ) or dl-LV 400 mg/m(2 ) followed by a FU bolus 400 mg/m(2 ) and 46-hour infusion 2,400 to 3,000 mg/m(2 ) every 46 hours every 2 weeks , either with irinotecan 180 mg/m(2 ) or with oxaliplatin 100 mg/m(2 ) as a 2-hour infusion on day 1 . At progression , irinotecan was replaced by oxaliplatin ( arm A ) , or oxaliplatin by irinotecan ( arm B ) . RESULT Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI ( P = .99 ) . Median second progression-free survival ( PFS ) was 14.2 months in arm A versus 10.9 in arm B ( P = .64 ) . In first-line therapy , FOLFIRI achieved 56 % response rate ( RR ) and 8.5 months median PFS , versus FOLFOX6 which achieved 54 % RR and 8.0 months median PFS ( P = .26 ) . Second-line FOLFIRI achieved 4 % RR and 2.5 months median PFS , versus FOLFOX6 which achieved 15 % RR and 4.2 months PFS . In first-line therapy , National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis , nausea/vomiting , and grade 2 alopecia were more frequent with FOLFIRI , and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6 . CONCLUSION Both sequences achieved a prolonged survival and similar efficacy . The toxicity profiles were different Background : The impact of thymidylate synthase ( TYMS ) and UDP-glucoronosyltransferase 1A ( UGT1A ) germline polymorphisms on the outcome of colorectal cancer ( CRC ) patients treated with irinotecan plus 5-fluorouracil ( irinotecan/5FU )  is still controversial . Our objective was to define a genetic-based algorithm to select patients to be treated with irinotecan/5FU . Methods : Genotyping of TYMS ( 5′TRP and 3′UTR ) , UGT1A1 * 28 , UGT1A9 * 22 and UGT1A7 * 3 was performed in 149 metastatic CRC patients treated with irinotecan/5FU as first-line chemotherapy enrolled in a r and omised phase 3 study . Their association with response , toxicity and survival was investigated by univariate and multivariate statistical analysis . Results : TYMS 3TRP/3TRP genotype was the only independent predictor of tumour response ( OR=5.87 , 95 % confidence interval (CI)=1.68–20.45 ; P=0.005 ) . UGT1A1 * 28/*28 was predictive for haematologic toxicity ( OR=6.27 , 95 % CI=1.09–36.12 ; P=0.04 ) , specifically for neutropenia alone ( OR=6.40 , 95 % CI=1.11–37.03 ; P=0.038 ) or together with diarrhoea ( OR=18.87 , 95 % CI=2.14–166.67 ; P=0.008 ) . UGT1A9 * 1/*1 was associated with non-haematologic toxicity ( OR=2.70 , 95 % CI=1.07–6.82 ; P=0.035 ) . Haplotype VII ( all non-favourable alleles ) was associated with non-haematologic toxicity ( OR=2.11 , 95 % CI=1.12–3.98 ; P=0.02 ) . Conclusion : TYMS and UGT1A polymorphisms influence on tumour response and toxicities derived from irinotecan/5FU treatment in CRC patients . A genetic-based algorithm to optimise treatment individualisation is proposed The aim of this study ( JGOG1063 ) was to determine the recommended dose ( RD ) for combination chemotherapy with irinotecan hydrochloride ( CPT-11 ) and nedaplatin ( NDP ) for advanced cervical squamous cell carcinoma .  CPT-11 was given intravenously in fixed doses of 60 mg/m2 on days 1 and 8 and NDP , in escalating doses , on day 1 , every 4 weeks . A total of 15 patients were enrolled in the study . At level 1 ( NDP : 50 mg/m2 ) , one of the 3 patients developed grade 3 diarrhea , so 3 additional patients were enrolled at this level . As none of the 3 additional patients exhibited dose-limiting toxicity , level 1 was elevated to level 2 ( NDP : 60 mg/m2 ) . The maximum tolerated dose was not reached , even at the highest dose level ( level 4 ; NDP : 80 mg/m2 ) . No further dose escalation was carried out , and level 4 ( CPT-11 : 60 mg/m2 , NDP : 80 mg/m2 ) was determined as the RD Purpose To investigate the activity of gemcitabine combined with irinotecan in patients with relapsed small cell lung cancer ( SCLC ) . Patients and methods SCLC patients who had experienced treatment failure with one prior chemotherapy were eligible . Patients were required to have a performance status of 0–2 and adequate organ function . Treatment consisted of gemcitabine ( 1,000 mg/m2 ) and irinotecan ( 150 mg/m2 ) on days 1 and 15 of a 28 day cycle . Results Thirty-one patients were enrolled and 30 patients received protocol treatment ( 10 had refractory disease and 20 had sensitive disease ) . The median age was 64 years , and the median performance status was one . An objective response was obtained in 36.7 % ( 95 % CI : 17.3.1–56.0 % ) of the patients . The median overall survival time was 14.4 months , and the 1 year survival rate was 51 % . The chief grade 3/4 toxicities included neutropenia ( 42 % ) , thrombocytopenia ( 3 % ) , diarrhea ( 9 % ) , and liver dysfunction ( 3 % ) . The only grade 4 toxicities were one case of grade 4 neutropenia ( 3.3 % ) and one case of grade 4 thrombocytopenia ( 3.3 % ) . Conclusion Gemcitabine plus irinotecan is an active regimen that seems to be well-tolerated by patients with previously treated SCLC Background : We investigated the efficacy and safety of biweekly irinotecan and cisplatin ( IP ) as first-line treatment in advanced gastric cancer patients . Methods : Irinotecan 125 mg/m2 on day 1 and cisplatin 60 mg/m2 on day 2 were administrated every 14 days . UGT1A1 * 28/*6 and toxicities were analyzed . Results : Forty-one eligible patients were enrolled . Fifteen patients , who were defined as the high-dose group , received starting doses of irinotecan 125 mg/m2 . Twenty-six patients , who were defined as the low-dose group , received starting doses of irinotecan 80 mg/m2 and cisplatin 50 mg/m2 . The response rate was 53.3 % in the irinotecan high-dose group and 53.8 % in the irinotecan low-dose group . The most common grade 3/4 toxicity was neutropenia ( 68.3 % ) . No significant difference in grade 3/4 neutropenia was found between patients with the wild-type genotype and those with variant genotypes for UGT1A1 * 28 or UGT1A1 * 6 . Conclusions : The combination of biweekly irinotecan 80 mg/m2 and cisplatin 50 mg/m2 was active and tolerable . The role of the UGT1A1 genotype in clinical toxicity of an IP regimen requires further investigation Background : To assess the efficacy and safety of individualised dose optimisation of irinotecan monotherapy as salvage treatment for advanced gastric cancer ( AGC ) . Methods : A total of 43 patients were enrolled .  Intravenous irinotecan ( 350 mg m−2 ) was administered every 3 weeks . The dose was increased ( 425 mg m−2 and 500 mg m−2 ) or decreased ( 250 mg m−2 ) depending on patient tolerance . UGT1A1 genotypes were determined by direct sequencing of genomic DNA extracted from peripheral blood . Results : A total of 183 cycles of irinotecan were administered , with a median of four cycles per patient . The overall response rate was 9.3 % , and the disease control rate was 62.8 % . Median time to disease progression was 2.8 months , and median overall survival was 8.0 months . Grade 3–4 neutropenia was the most common toxicity ( 53.5 % ) , and febrile neutropenia was the least common toxicity ( 4.6 % ) . Compared with defective allele groups , UGT1A1 * 1/*1 was associated with a lower incidence of grade 3–4 neutropenia during the first cycle ( P=0.018 ) . Conclusion : Individualised irinotecan dose escalation based on patient tolerance was not associated with increased toxicity and shows modest activity as salvage chemotherapy for AGC . The role of UGT1A1 genotype in clinical toxicity requires further evaluation Irinotecan‐induced severe neutropenia is associated with homozygosity for the UGT1A1 * 28 or UGT1A1 * 6 alleles . In this study , we determined the maximum‐tolerated dose ( MTD ) of irinotecan in patients with UGT1A1 polymorphisms . Patients who had received chemotherapy other than irinotecan for metastatic gastrointestinal cancer were enrolled . Patients were divided into three groups according to UGT1A1 genotypes : wild‐type ( * 1/*1 ) ; heterozygous ( * 28/*1 , * 6/*1 ) ; or homozygous ( * 28/*28 , * 6/*6 , * 28/*6 ) . Irinotecan was given every 2 weeks for two cycles . The wild‐type group received a fixed dose of irinotecan ( 150 mg/m2 ) to serve as a reference . The MTD was guided from 75 to 150 mg/m2 by the continual re assessment method in the heterozygous and homozygous groups . Dose‐limiting toxicity ( DLT ) and pharmacokinetics were evaluated during cycle 1 . Of 82 patients enrolled , DLT was assessable in 79 patients ( wild‐type , 40 ; heterozygous , 20 ; and homozygous , 19 ) . Dose‐limiting toxicity occurred in one patient in the wild‐type group , none in the heterozygous group , and six patients ( grade 4 neutropenia ) in the homozygous group . In the homozygous group , the MTD was 150 mg/m2 and the probability of DLT was 37.4 % . The second cycle was delayed because of neutropenia in 56.3 % of the patients given the MTD . The AUC0–24 h of SN‐38 was significantly greater ( P < 0.001 ) and more widely distributed in the homozygous group . Patients homozygous for the UGT1A1 * 28 or UGT1A1 * 6 allele can receive irinotecan in a starting dose of 150 mg/m2 , but many required dose reductions or delayed treatment in subsequent cycles . UMIN Clinical Trial Registration number : UMIN000000618 . ( Cancer Sci 2011 ; 102 : 1868–1873 Introduction : Paclitaxel plus carboplatin ( TC ) is generally considered to be the " gold st and ard " regimen for treatment of epithelial ovarian carcinomas . Little data are available , however , on the use of this regimen in patients with clear cell adenocarcinoma of the ovary ( CCC ) . Combination chemotherapy with irinotecan hydrochloride plus cisplatin has been reported to be effective for primary and recurrent or resistant CCC . We compared these 2 combinations in patients with CCC . Methods : Patients ( 
    Output:
    
In conclusion , in this meta- analysis , the UGT1A1 * 6 polymorphisms were associated with an increased risk of IRI-induced neutropenia in cancer patients , and increased incidences of severe neutropenia could be correlated with diverse regions , cancer type , low dose of IRI and the duration of treatment