***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 : Inherited variations in drug metabolizing enzymes may influence drug efficacy . This phase II study assesses the impact of second-line weekly irinotecan (CPT-11)/docetaxel in non-small cell lung cancer ( NSCLC ) patients , and gauges the uridine diphosphate glucuronosyl transferase ( UGT1A1 ) polymorphism influence in toxicity and antitumor activity . Experimental Design : Fifty-one patients with NSCLC treated with at least one prior chemotherapy regimen were enrolled . Patients received irinotecan 70 mg/m2 followed by docetaxel 25 mg/m2 . Both drugs were given on days 1 , 8 , and 15 every 28 days . UGT1A1 polymorphism were analyzed in blood sample s of 47 patients . The UGT1A1 polymorphism are classified according to the number of TA repeats in the promoter region of this gene . Results : Three patients ( 6 % ) achieved a partial response and nineteen patients ( 37 % ) had stable disease . Median survival was 8 months ( 95 % CI : 4.8–11.2 ) and 1-year survival 30 % . Grade 3–4 hematologic toxicity was low ( less than 10 % of patients ) ; 15 % of patients had grade 3 asthenia and 25 % of patients had grade 3/4 diarrhea . The frequency of UGT1A1 genotypes was as follows : 6/6 49 % , 6/7 36 % , and 7/7 15 % . No differences in toxicity were observed according to UGT1A1 polymorphism . A nonsignificant improvement in time to progression ( 4 vs. 3 months ) and median survival ( 11 vs. 8 months ) was detected in patients with the variant alleles ( 6/7 and 7/7 ) . Conclusions : This weekly irinotecan/docetaxel regimen has shown an acceptable toxicity profile while encouraging median and 1-year survival in heavily pretreated NSCLC patients . The tendency to better prognosis in patients carrying the variant genotypes 6/7 and 7/7 of UGT1A1 gene requires further validation 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 PURPOSE Capecitabine and irinotecan are commonly used in the treatment of metastatic colorectal cancer ( CRC ) . We hypothesized that germline polymorphisms within genes related to drug target ( thymidylate synthase ) or metabolizing enzymes ( UDP-glucuronosyltransferase , UGT ) would impact response and toxicity to the combination of capecitabine plus irinotecan ( CPT-11 ) . EXPERIMENTAL DESIGN Sixty-seven patients with measurable CRC were treated with irinotecan i.v . ( 100 or 125 mg/m(2 ) ) on days 1 and 8 and capecitabine orally ( 900 or 1,000 mg/m(2 ) , twice daily ) on days 2 through 15 of each 3-week cycle . Genomic DNA was extracted from peripheral blood and genotyped using Pyrosequencing , GeneScan , and direct sequencing ( Big Dye terminator ) technologies . RESULTS The overall objective response rate was 45 % with 21 patients ( 31 % ) exhibiting grade 3 or 4 diarrhea and 3 patients ( 4.5 % ) demonstrating grade 3 or 4 neutropenia in the first two cycles . Low enzyme activity UGT1A7 genotypes , UGT1A7 * 2/*2 ( six patients ) and UGT1A7 * 3/*3 ( seven patients ) , were significantly associated with antitumor response ( p = 0.013 ) and lack of severe gastrointestinal toxicity ( p = 0.003 ) . In addition , the UGT1A9 -118 (dT)(9/9 ) genotype was significantly associated with reduced toxicity ( p = 0.002 ) and increased response ( p = 0.047 ) . There were no statistically significant associations between UGT1A1 , UGT1A6 , or thymidylate synthase genotypes and toxicity or tumor response . CONCLUSIONS These data strongly suggest that UGT1A7 and /or UGT1A9 genotypes may be predictors of response and toxicity in CRC patients treated with capecitabine plus irinotecan . Specifically , patients with genotypes conferring low UGT1A7 activity and /or the UGT1A9 (dT)(9/9 ) genotype may be particularly likely to exhibit greater antitumor response with little toxicity The primary end point of the study was the analysis of associations between polymorphisms with putative influence on  5-fluorouracil/irinotecan activity and progression-free survival ( PFS ) of patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy .  Peripheral blood sample s from 146 prospect ively enrolled patients were used for genotyping polymorphisms in thymidylate synthase ( TS ) , methylenetetrahydrofolate reductase ( MTHFR ) , excision repair cross-complementation group-1 ( ERCC 1 ) xeroderma pigmentosum group-D ( XPD ) , X-ray cross-complementing-1 ( XRCC 1 ) , X-ray cross-complementing-3 ( XRCC 3 ) and uridine diphosphate-glucuronosyltransferases-A1 ( UGT1 A1 ) . TS 3′-UTR 6+/6 + and XRCC3 - 241 C/C genotypes were associated with adverse PFS . Hazard ratio for PFS achieved 2.89 ( 95 % confidence interval=1.56–5.80 ; P=0.002 ) in 30 patients ( 20 % ) with both risk genotypes . Risk for Grade III – IV neutropenia was significantly associated with UGT1A1 * 28 7/7 genotype . These promising findings deserve further investigations and their validation in independent prospect i ve studies Purpose : We conducted a phase II study of carboplatin and irinotecan in patients with advanced non-small cell lung cancer ( NSCLC ) . In addition , we studied the correlation between certain genotypes of enzymes involved in irinotecan metabolism with efficacy and toxicity . Patients and Methods : Patients with stage IIIB , IV , or recurrent NSCLC received a combination of irinotecan and carboplatin every 3 weeks at a dose of 200 mg/m2 and area under the curve of 5 . Pharmacogenomic analysis was performed on several genes of interest ( ABCB1 , CYP3A4 * 1B , ERCC2 , GSTP1 , UGT1A1 * 28 , and XRCC1 ) . Results : Forty-two patients enrolled between December 2001 and January 2004 . Six patients achieved partial responses ( 14 % ) , and 19 ( 45 % ) had stable disease . The median progression-free survival was 6.9 months . The median overall survival was 11.7 months , with 1-year overall survival of 42 % . The most common toxicities were hematologic ; grade 3 or 4 neutropenia was experienced by 26 patients ( 62 % ) during treatment , and 15 patients ( 36 % ) experienced grade 3 or 4 thrombocytopenia . The homozygous UGT1A1 * 28 ( 7/7 ) genotype was associated with grade 4 neutropenia in three of four patients ( 75 % ) , but only eight out of 30 ( 27 % ) with 6/6 or 6/7 genotypes experienced grade 4 neutropenia ( p = 0.09 ) . None of the 14 patients with the GSTP1 I105V A/A genotype had a partial response , as opposed to five out of 19 ( 26 % ) of those with the G/A or G/G genotypes ( p = 0.057 ) . Conclusion : The combination of carboplatin and irinotecan is an active combination in NSCLC , with response rates comparable with other platinum-containing doublets . Further studies with irinotecan should incorporate prospect i ve pharmacogenomic analysis to identify markers for response and toxicity PURPOSE C and i date predictive biomarkers for irinotecan and oxaliplatin were assessed in 1,628 patients in Fluorouracil , Oxaliplatin , CPT-11 : Use and Sequencing ( FOCUS ) , a large r and omized trial of  fluorouracil alone compared with fluorouracil and irinotecan and compared with fluorouracil and oxaliplatin in advanced colorectal cancer . METHODS The c and i date biomarkers were : tumor immunohistochemistry for MLH1/MSH2 , p53 , topoisomerase-1 ( Topo1 ) , excision repair cross-complementing gene 1 ( ERCC1 ) , O-6-methylguanine-DNA-methyltranserase ( MGMT ) , and cyclooxygenase 2 ( COX2 ) ; germline DNA polymorphisms in GSTP1 , ABCB1 , XRCC1 , ERCC2 , and UGT1A1 . These were screened in more than 750 patients for interaction with benefit from irinotecan or oxaliplatin ; two markers ( Topo1 and MLH1/MSH2 ) met criteria to be taken forward for analysis in the full population . Primary end points were progression-free survival ( PFS ) and overall survival . RESULTS One thous and three hundred thirteen patients ( 81 % ) were assessable for Topo1 immunohistochemistry ( low , < 10 % ; moderate , 10 % to 50 % ; or high , > 50 % tumor nuclei ) . In patients with low Topo1 , PFS was not improved by the addition of either irinotecan ( hazard ratio [ HR ] , 0.98 ; 95 % CI , 0.78 to 1.22 ) or oxaliplatin ( HR , 0.85 ; 95 % CI , 0.68 to 1.07 ) ; conversely , patients with moderate/high Topo1 benefited from the addition of either drug ( HR , 0.48 to 0.70 in all categories ; interaction P = .005 ; overall , P = .001 for irinotecan ; P = .05 for oxaliplatin ) . High Topo1 was associated with a major overall survival benefit with first-line combination chemotherapy ( HR , 0.60 ; median benefit , 5.3 months ) ; patients with moderate or low Topo1 did not benefit ( HR , 0.92 and 1.09 , respectively ; interaction P = .005 ) . MLH1/MSH2 did not show significant interaction with treatment , although the low rate of loss ( 4.4 % ) limits the power of the study for this biomarker . CONCLUSION Topo1 immunohistochemistry identified sub population s that did or did not benefit from irinotecan , and possibly also from oxaliplatin . If verified independently , this information will contribute to the individualization of treatment for colorectal cancer e15580 Background : Pharmacogenetic advances in cancer chemotherapy have the potential to predict clinical benefit to particular regimens . 
    Output:
    
Irinotecan dose also did not impact upon ORR differences between UGT1A1 genotype groups .
An individual 's response to irinotecan is unlikely to be affected by UGT1A1 * 28 status