UDP-glucuronosyltransferase (UGT) 1A1*28 polymorphism-directed phase II study of irinotecan with 5'-deoxy-5-fluorouridine (5'-DFUR) for metastatic colorectal cancer.

Abstract

AIM:

We performed a phase II study of irinotecan with 5'-deoxy-5-fluorouridine (5'-DFUR) for metastatic colorectal cancer based on UDP-glucuronosyltransferase (UGT) 1A1 polymorphism.

PATIENTS AND METHODS:

A total of 28 patients were enrolled. The dose of irinotecan was 150 mg/m(2) for patients with the *1/*1 wild-type genotype, and 70 mg/m(2) for those with the *1/*28 mutated genotype. The primary end-point was the response rate (RR); secondary end-points were safety, time to treatment failure (TTF), and overall survival (OS).

RESULTS:

In 28 patients total, genotype was wild-type in 22 and mutated in six. The RR was *1/*1 (22.7%; wild-type) vs. *1/*28 (16.7%; mutated); the median TTF was 5 months vs. 4.5 months, and the median OS was 13 months vs. 17.5 months, respectively. None of these differences were significant. Toxicities of grade 3 or higher were neutropenia (9.0% vs. 0%, respectively) and diarrhea (13.6% vs. 0%, respectively).

CONCLUSION:

This genotype-oriented therapy was effective and safe, and thus appears useful for patients who have complications or advanced age.

• Authors: Shinsuke Kanekiyo, Shoichi Hazama, Hiroshi Kondo, Atsushi Nagashima, Ryuichi Eto, Shin Yoshida, Ryoichi Shimizu, Atsuhiro Araki, Tatsuhito Yamamoto, Tetsuji Uchiyama, Shigefumi Yoshino, Naoko Okayama, Yuji Hinoda, Masaaki Oka
• Journal: Anticancer research (Anticancer Res) Vol. 33 Issue 8 Pg. 3423-30 (Aug 2013) ISSN: 1791-7530 [Electronic] Greece
• PMID: 23898114 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Floxuridine
• Irinotecan
• UGT1A1 enzyme
• Glucuronosyltransferase
• doxifluridine
• Camptothecin

Topics

• Aged
• Antineoplastic Agents (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Camptothecin (adverse effects, analogs & derivatives, therapeutic use)
• Colorectal Neoplasms (drug therapy, enzymology, genetics, pathology)
• Female
• Floxuridine (adverse effects, analogs & derivatives, therapeutic use)
• Glucuronosyltransferase (genetics)
• Humans
• Irinotecan
• Male
• Middle Aged
• Neoplasm Metastasis
• Polymorphism, Genetic
• Survival Analysis
• Time Factors
• Treatment Outcome