RESUMO
Background and purpose: Uridine diphosphoglucu-ronosyl transferase 1A1 (UGT1A1) is an important enzyme for metabolism of irinotecan. The activity of UGT1A1 enzyme was significantly affected by the gene polymorphism. This study aimed to investigate the correlation of UGT1A1*28 and *6 gene polymorphisms with irinotecan-based chemotherapy in colorectal cancer(CRC). Methods: Analysis of UGT1A1*28 and *6 gene polymorphisms was performed in 160 gastrointestinal cancer patients admitted to Zhongshan Hospital Fudan University from Apr. 2013 to Dec. 2013 by amplifying the gene fragments using PCR, STR and Sanger sequencing. Eighty-two cases with CRC treated with irinotecan were chosen to observe the adverse events during chemotherapy. The incidence of different genotypes was compared. Results:The distribution of the genotypes in 160 gastrointestinal cancer patients was as followed:UGT1A1*28 wild-type genotype TA6/6 (124, 77.5%), heterozygous genotype TA6/7 (33, 20.5%), and homozygous genotype TA7/7 (3, 2.0%);UGT1A1*6 wild-type genotype GG (105, 65.6%), heterozygous genotype GA (48, 30.0%), and homozygous genotype AA (7, 4.4%). In the 82 CRC cases, the incidences of grade 3 and 4 neutropenia in the patients carrying UGT1A1*28 (TA6/7+TA7/7 ) were higher than those in the WT genotype (TA6/6) (58.3%vs 0.0, P<0.001), and increased the total incidence of adverse events (76.0%vs 45.6%, P<0.001). There was no signiifcant relevance between UGT1A1*6 genotype, age, gender chemotherapy and adverse events. Conclusion:In the CRC cases with irinotecan-based chemotherapy, the UGT1A1*28 (TA6/7+TA7/7) genotype signiifcantly increased the risk of grade 3 and 4 neutropenia. Detecting UGT1A1 gene polymorphisms may guide individualized treatment and predict adverse events.
RESUMO
Background and purpose: Cetuximab-containing regimen has been increasingly applied in the treatment of patients with metastatic colorectal cancer. Simultaneously, the predictive factors of outcome for cetuximab have been thoroughly researched. The aim of this study was to evaluate the relationship between K-ras status and efficacy of cetuximab containing regimen in the treatment of patients with metastatic eolorectal cancer. Methods: Between March 2006 and June 2008, twenty-seven patients with metastatic colorectal cancer were treated with cetuximab in combination with chemotherapy. The K-ras mutation status [wild-type (wt) or mutation (nat)] was examined by polymerase chain reaction (PCR) and direct sequencing. The influence of K-ras mutation status on efficacy of cetuximab-containing regimen was analyzed. Results: For 27 patiants in this cohort, K-ras wt was detected in 55.6% (15/27) cases and K-ras mt in 44.4% (12/27) cases. Statistically significant differences were found between the patients with K-ras wt and K-ras mt in terms of overall response rate (ORR) (66.7% vs 25.0%,P=0.035) and progression-free survival (PFS) (8 months vs 4 months, P=0.0028). However, there was no significant difference in overall survival (OS) (19 months vs 12 months, P>0.05). The most common treatment-related adverse effect was skin reaction, with incidence rate of 80.0% and 66.7% (P>0.05), respectively. No treatment related death was observed. Conclusion: K-ras mutation status is a predictive factor of good efficacy of cetuximab-containing regimen in the treatment of patients with metastatic colorectal cancer. Patients with K-ras wt could benefit from cetuximab in combination with chemotherapy.