***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 
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    Input: Purpose : Oxaliplatin displays a frequent dose-limiting neurotoxicity due to its interference with neuron voltage-gated sodium channels through one of its metabolites , oxalate , a calcium chelator . Different clinical approaches failed in neurotoxicity prevention , except calcium-magnesium infusions . We characterized oxalate outcome following oxaliplatin administration and its interference with cations and amino acids . We then looked for genetic predictive factors of oxaliplatin-induced neurotoxicity . Experimental Design : We first tested patients for cations and oxalate levels and did amino acid chromatograms in urine following oxaliplatin infusion .  In the second stage , before treatment with FOLFOX regimen , we prospect ively looked for variants in genes coding for the enzymes involved ( a ) in the oxalate metabolism , especially glyoxylate aminotransferase ( AGXT ) , and ( b ) in the detoxification glutathione cycle , glutathione S-transferase π , and for genes coding for membrane efflux proteins ( ABCC2 ) . Results : In the first 10 patients  , urinary excretions of oxalate and cations increased significantly within hours following oxaliplatin infusion , accompanied by increased excretions of four amino acids ( glycine , alanine , serine , and taurine ) linked to oxalate metabolism . In a further 135 patients , a minor haplotype of AGXT was found significantly predictive of both acute and chronic neurotoxicity . Neither glutathione S-transferase π nor ABCC2 single nucleotide polymorphisms we looked for were linked to neurotoxicity . Conclusion : These data confirm the involvement of oxalate in oxaliplatin neurotoxicity and support the future use of AGXT genotyping as a pretherapeutic screening test to predict individual susceptibility to neurotoxicity BACKGROUND Oxaliplatin neurosensory toxicity is dose limiting and may present as acute symptoms and /or cumulative peripheral neuropathy . PATIENTS AND METHODS From October 2005 to May 2008 , patients with oxaliplatin-induced acute neurotoxicity were r and omized into a double-blind study , to receive either venlafaxine 50 mg 1 h prior oxaliplatin infusion and venlafaxine extended release 37.5 mg b.i.d . from day 2 to day 11 or placebo .  Neurotoxicity was evaluated using numeric rating scale ( NRS ) for pain intensity and experienced relief under treatment , the Neuropathic Pain Symptom Inventory and the oxaliplatin-specific neurotoxicity scale . The primary end point was the percentage of patients with a 100 % relief under treatment . RESULTS Forty-eight patients were included ( 27 males , median age : 67.6 years ) . Most patients had colorectal cancer ( 72.9 % ) . Median number of cycles administered at inclusion was 4.5 ( mean cumulative oxaliplatin dose : 684.6 mg ) . Twenty out of 24 patients in arm A ( venlafaxine ) and 22 out of 24 patients in arm B ( placebo ) were assessable for neurotoxicity . Based on the NRS , full relief was more frequent in the venlafaxine arm : 31.3 % versus 5.3 % ( P=0.03 ) . Venlafaxine side-effects included grade 1 - 2 nausea ( 43.1 % ) and asthenia ( 39.2 % ) without grade 3 - 4 events . CONCLUSION Venlafaxine has clinical activity against oxaliplatin-induced acute neurosensory toxicity The discovery of pharmacogenomic markers in colorectal cancer ( CRC ) could be setting -specific . FOLFOX4 is employed in the adjuvant and metastatic setting in CRC . This prospect i ve study is aim ed to vali date in the adjuvant setting the pharmacogenomic markers of toxicity reported in the metastatic setting ( that is , GSTP1-rs947894 , and -rs1138272 ; GSTM1-null genotype ; AGXT-rs4426527 , -rs34116584 and del-74 bp ) , and to discover additional markers . CRC patients ( n=144 ) treated with adjuvant FOLFOX4 were genotyped for 57 polymorphisms in 29 genes .  Grade ⩾2 neurotoxicity was associated ( false discovery rate-adjusted q-value < 0.1 ) with single-nucleotide polymorphisms in ABCC1 ( rs2074087 : odds ratio=0.43(0.22–0.86 ) ) , and ABCC2 ( rs3740066 : 2.99(1.16–7.70 ) ; rs1885301 : 3.06(1.35–6.92 ) ; rs4148396 : 4.69(1.60–13.74 ) ; rs717620 : 14.39(1.63–127.02 ) ) . hMSH6-rs3136228 was associated with grade 3–4 neutropenia ( 3.23(1.38–7.57 ) , q-value=0.0937 ) . XRCC3-rs1799794 was associated with grade 3–4 non-hematological toxicity ( 8.90(2.48–31.97 ) , q-value=0.0150 ) . The markers previously identified in metastatic CRC were not vali date d. We have identified new markers of toxicity in genes of transport and DNA repair . If vali date d in other studies , they could help to identify patients at risk of toxicity PURPOSE Oxaliplatin is detoxified by conjugation to glutathione via the enzyme Glutathione-S-transferase pi ( GSTP1 ) . The aim of this study is to investigate the association of GSTP1 Ile105Val genetic polymorphism with oxaliplatin efficacy and toxicity in advanced colorectal cancer ( ACC ) patients . EXPERIMENTAL DESIGN A total of 91 ACC patients received capecitabine and oxaliplatin ( CAPOX ) as a part of a multicentre phase-III study of the Dutch Colorectal Cancer Group . Tumour response was evaluated according to RECIST , toxicity was grade d using CTC , and GSTP1 Ile105Val was determined by pyrosequencing . RESULTS Overall survival after CAPOX was similar for patients with the Ile/Ile ( 11.5 mo ) , Ile/Val ( 11.6 mo ) and Val/Val ( 12.6 mo ) genotypes ( p=0.602 ) . Likewise , there were no statistically significant differences in progression-free survival ( p=0.252 ) . Overall grade s 3 - 4 toxicity was not related to genotype ( p=0.313 ) . There were no differences in any grade or grade s 3 - 4 neurotoxicity amongst the patients who received > or = 500 mg/m(2 ) of oxaliplatin ( p-values of 0.376 and 0.772 , respectively ) . CONCLUSIONS The results of this study indicate that the GSTP1 genotype is not predictive for progression-free survival or overall survival in ACC patients treated with CAPOX . Moreover , overall neurotoxicity and neurotoxicity in patients receiving 500 mg/m(2 ) of oxaliplatin was not associated with GSTP1 genotype PURPOSE The objective is to investigate whether polymorphisms with putative influence on fluorouracil/oxaliplatin activity are associated with clinical outcomes of patients with advanced colorectal cancer treated with first-line oxaliplatin , folinic acid , and fluorouracil palliative chemotherapy .  MATERIAL S AND METHODS Consecutive patients were prospect ively enrolled onto medical oncology units in Central Italy . Patients were required to have cytologically/histologically confirmed metastatic disease with at least one measurable lesion . Peripheral blood sample s were used for genotyping 12 polymorphisms in thymidylate synthase , methylenetetrahydrofolate reductase , xeroderma pigmentosum group D ( XPD ) , excision repair cross complementing group 1 ( ERCC1 ) , x-ray cross complementing group 1 , x-ray cross complementing protein 3 , glutathione S-transferases ( GSTs ) genes . The primary end point of the study was to investigate the association between genotypes and progression-free survival ( PFS ) . RESULTS In 166 patients , ERCC1 - 118 T/T , XPD-751 A/C , and XPD-751 C/C genotypes were independently associated with adverse PFS . The presence of two risk genotypes ( ERCC1 - 118 T/T combined with either XPD-751 A/C or XPD-751 C/C ) occurred in 50 patients ( 31 % ) . This profiling showed an independent role for unfavorable PFS with a hazard ratio of 2.84 % and 95 % CI of 1.47 to 5.45 ( P = .002 ) . Neurotoxicity was significantly associated with GSTP1 - 105 A/G. Carriers of the GSTP1 - 105 G/G genotype were more prone to suffer from grade 3 neurotoxicity than carriers of GSTP1 - 105 A/G and GSTP1 - 105 A/A genotypes . CONCLUSION A pharmacogenetic approach may be an innovative strategy for optimizing palliative chemotherapy in patients with advanced colorectal cancer . These findings deserve confirmation in additional prospect i ve studies 
    Output:
    
Conclusion This meta- analysis did not support the hypothesis that GSTP1 Ile105Val polymorphism was related to the occurrence of  neurotoxicity  in oxaliplatin-treated patients .