Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker

Keam, Bhumsuk; Im, Seock‐Ah; Han, Sae‐Won; Ham, Hye Seon; Kim, Min A; Oh, Do‐Youn; Lee, Se‐Hoon; Kim, Jee Hyun; Kim, Dong-Wan; Kim, Tae-You; Heo, Dae Seog; Kim, Woo Ho; Bang, Yung‐Jue

doi:10.1186/1471-2407-8-148

Cited by 66 publications

(62 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several studies on TYMS expression and this polymorphism were reported especially in colorectal cancer, with some clinical studies showing favorable results in 2R/2R (32)(33)(34). However, two recent studies in advanced gastric cancer did not show any significant impact of this polymorphism as seen with our results (7,9). Although further studies may be necessary, the clinical significance of this polymorphism may be limited.…”

Section: Discussioncontrasting

confidence: 47%

“…5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism, which catalyzes the irreversible conversion of 5-10-methylene tetrahydrofolate to 5-methyltetrahydrofolate (5). Because decreased activity of MTHFR may result in accumulation of 5-10-methylene tetrahydrofolate and improve the antitumor efficacy of FU, several studies evaluated genetic polymorphisms of MTHFR, with or without genetic polymorphisms of TYMS in patients with advanced gastric cancer, although the clinical data are still controversial (6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Folate Intake along with Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase in Patients with Advanced Gastric Cancer

Shitara

Muro

Ito

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Background: A relationship between dietary folate intake and efficacy of fluorouracil (FU) is supported by preclinical data. Furthermore, there are several reports that evaluated genetic polymorphisms of MTHFR (methylenetetrahydrofolate reductase) or TYMS (thymidylate synthase) and efficacy of FU. However, to our knowledge, there are no reports that evaluate simultaneously the effects of folate intake and genetic polymorphisms on clinical outcome of gastric cancer patients.Methods: We retrospectively analyzed the survival impact of estimated folate intake by a food frequency questionnaire and MTHFR and TYMS polymorphisms in 132 patients with advanced gastric cancer who were treated with first-line FU-based chemotherapy.Results: Median overall survival was 11.3 months (95% confidence interval, 9.4-13.4 mo) and median progression-free survival was 5.2 months (95% confidence interval, 4.1-6.3 mo). Patients with folate intake of >260 μg/day (n = 88) showed longer overall survival compared with low folate intake (n = 44; overall survival, 12.2 versus 8.4 mo). In a multivariate Cox model, patients who had folate intake of >260 μg/day, MTHFR 677 TT polymorphism, and TYMS-3′ untranslated region 6-bp insertion were associated with better survival. Similar tendency was observed in progression-free survival. No interaction was observed between folate intake and favorable genotypes.Conclusion: Folate intake and genetic polymorphisms of MTHFR and TYMS were associated with better clinical outcome by FU-based chemotherapy in advanced gastric cancer.Impact: Our results suggested folate intake and folate-related genetic polymorphisms may play an important role in efficacy of FU-based chemotherapy in advanced gastric cancer. Cancer Epidemiol Biomarkers Prev;

show abstract

Section: Discussioncontrasting

confidence: 47%

Section: Introductionmentioning

confidence: 99%

Folate Intake along with Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase in Patients with Advanced Gastric Cancer

Shitara

Muro

Ito

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

show abstract

“…An essential member of the NER pathway is XPD, which is a key rate-limiting enzyme in NER and works as an ATP-e. Previous studies have indicated that the XPD Lys751Gln polymorphism is associated with suboptimal DRC and determined the effects on clinical outcomes of oxaliplatinbased regimens in CRC (Park et al, 2001;Stoehlmacher et al, 2004), esophageal cancer (Leichman et al, 2011) and gastric cancer (Keam et al, 2008). Therefore, the functional XPD Lys751Gln polymorphism may reveal the mechanism to resistance to oxaliplatin and serve as a useful predictive biomarker.…”

Section: Discussionmentioning

confidence: 99%

The XPD Lys751Gln Polymorphism has Predictive Value in Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Systemic Review and Meta-analysis

Qian

Liu²,

Pei³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: The predictive value of the xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism regarding clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, but the results remain inconclusive. Therefore, we performed a meta-analysis to determine the precise role of the XPD Lys751Gln polymorphism in this clinical situation and optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs), generalized odds ratio (ORG) and their 95% confidence intervals (CIs) were used to estimate the objective response, while hazard ratios (HRs) with 95%CIs were used for progression-free survival (PFS) and overall survival (OS). Results: A total of 17 studies including 2,286 patients met the inclusion criteria. Overall, the XPD 751Gln allele was associated with a non-significant reduced objective response to oxaliplatin-based chemotherapy in all patients or in the Asian and Caucasian subgroups.

show abstract

“…However, other studies on lung cancer [10] and colorectal cancer [9,11,20,21] showed opposite results. In addition, several studies demonstrated that no clear association was found between ERCC1 codon 118 polymorphism and platinum sensitivity [24][25][26] . In a recent study on advanced gastric cancer treated with fluorouracil/cisplatin palliative chemotherapy, a tendency to higher response rate was found in patients with C allele (P = 0.09).…”

Section: Discussionmentioning

confidence: 99%

ERCC1 polymorphism, expression and clinical outcome of oxaliplatin-based adjuvant chemotherapy in gastric cancer

Huang¹,

Dong²,

Du³

et al. 2008

WJG

View full text Add to dashboard Cite

in gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy (P < 0.05).CONCLUSION: ERCC1 codon 118 polymorphism has no significant impact on ERCC1 mRNA expression, and the intratumoral ERCC1 mRNA level but not codon 118 polymorphism may be a useful predictive parameter for the relapse and survival of gastric cancer patients receiving oxaliplatin-based adjuvant chemotherapy. INTRODUCTIONIn China, gastric cancer is the leading cause of cancer deaths, accounting for nearly one-fourth of all cancer deaths. Surgery is the primary modality for managing early-stage and locally-advanced disease. However, even after gastrectomy, the majority of patients develop local or distant recurrence [1] . Adjuvant chemotherapy for gastric cancer has been under clinical investigation for more than four decades. Fluoropyrimidines, platinumdrugs and taxanes were shown to be effective in the treatment of gastric cancer. However, the response rates of these drugs or their combinations were less than 50% [2,3] . There is no standard regimen for postoperative treatment at the moment. Having an effective assay to predict the response to a given chemotherapeutic protocol beforehand would greatly enhance the success rate as well as the life quality of the patients.The nucleotide excision repair (NER) system plays a significant role in repairing a variety of distorting Abstract AIM: To determine the influence of excision repair cross complementing group 1 (ERCC1 ) codon 118 polymorphism and mRNA level on the clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy. METHODS: Eighty-nine gastric cancer patients treated with oxalipatin-based adjuvant chemotherapy were included in this study. ERCC1 codon 118 C/T polymorphism was tested by polymerase chain reaction-ligation detection reaction (PCR-LDR) method in peripheral blood lymphocytes of those patients; and the intratumoral ERCC1 mRNA expression was measured using reverse transcription PCR in 62 patients whose tumor tissue specimens were available. RESULTS: No significant relationship was found between ERCC1 codon 118 polymorphism and ERCC1 mRNA level. The median relapse-free and overall survival period was 20.1 mo and 28.4 mo, respectively. The relapse-free and overall survivals in patients with low levels of ERCC1 mRNA were significantly longer than those in patients with high levels (P < 0.05), while there was no significant association found between ERCC1 118 genotypes and the disease prognosis. Multivariate analysis also showed that ERCC1 mRNA level was a potential predictor for relapse and survival

show abstract

Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker

Cited by 66 publications

References 43 publications

Folate Intake along with Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase in Patients with Advanced Gastric Cancer

Folate Intake along with Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase in Patients with Advanced Gastric Cancer

The XPD Lys751Gln Polymorphism has Predictive Value in Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Systemic Review and Meta-analysis

ERCC1 polymorphism, expression and clinical outcome of oxaliplatin-based adjuvant chemotherapy in gastric cancer

Contact Info

Product

Resources

About