Uridine diphosphate glucuronide transferase 1A1FNx0128 gene polymorphism and the toxicity of irinotecan in recurrent and refractory small cell lung cancer.

Abstract

OBJECTIVE:

The aim was to investigate the association between uridine diphosphate glucuronide transferase 1A1 (UGT1A1) gene promoter region polymorphism and irinotecan-related adverse effects and efficacy on recurrent and refractory small cell lung cancer (SCLC).

MATERIALS AND METHODS:

A total of 31 patients with recurrent and refractory SCLC were enrolled in this study from June 2012 to August 2013 and received at least two cycles of single-agent irinotecan chemotherapy. The efficacy and adverse effects of irinotecan were evaluated. DNA was extracted from peripheral blood and direct sequencing method was employed to test UGT1A1FNx0128 polymorphism, thus analyzing the correlation between UGT1A1FNx0128 polymorphism and irinotecan-related side-effects and efficacy.

RESULTS:

A total of 25 cases (80.6%) were UGT1A1FNx0128 wild-type (TA) 6 /(TA) 6 ; 6 cases (19.4%) were heterozygous mutant (TA) 6 /(TA) 7 , no homozygous mutant genotype (TA) 7 /(TA) 7 was found. The incidences of grade 3/4 neutropenia, diarrhea and thrombocytopenia were 35.5%, 25.8% and 22.6% in all the patients, respectively. The incidence of 3/4 adverse effects in patients with genotype (TA) 6 /(TA) 6 and heterozygous (TA) 6 /(TA) 7 had no statistical difference (P > 0.05 for all). The overall response rate (ORR) was 32.3%. Median progression free survival (PFS) and overall survival (OS) were 4 months and 7.5 months in all patients, respectively. There was no statistical difference in ORR, PFS and OS between genotype (TA) 6 /(TA) 6 patients and heterozygous (TA) 6 /(TA) 7 patients.

CONCLUSION:

Irinotecan showed efficacy in patients with recurrent and refractory SCLC; UGT1A1 FNx01 28 polymorphism failed to predict the incidence of serious adverse effects and efficacy of irinotecan.

• Authors: Fan Yun, Miao Lulu, Huang Zhiyu, Gong Lei, Yu Haifeng, Lei Tao, Yang Haiyan, Xie Conghua
• Journal: Journal of cancer research and therapeutics (J Cancer Res Ther) Vol. 10 Suppl Pg. C195-200 (Nov 2014) ISSN: 1998-4138 [Electronic] India
• PMID: 25450281 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Irinotecan
• UGT1A1 enzyme
• Glucuronosyltransferase
• Camptothecin

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Camptothecin (analogs & derivatives, therapeutic use)
• Female
• Genotype
• Glucuronosyltransferase (genetics)
• Humans
• Irinotecan
• Lung Neoplasms (drug therapy, genetics, pathology)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (genetics, pathology)
• Polymorphism, Genetic (genetics)
• Promoter Regions, Genetic (genetics)
• Small Cell Lung Carcinoma (drug therapy, genetics, pathology)
• Young Adult