Favorable genetic polymorphisms predictive of clinical outcome of chemoradiotherapy for stage II/III esophageal squamous cell carcinoma in Japanese.

Abstract

OBJECTIVES:

This study was performed to find the genetic factors predictive of clinical outcome to a 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT) in Japanese patients with locally advanced esophageal squamous cell carcinoma (ESCC).

MATERIALS AND METHODS:

Thirty-one patients with stage I-IVa ESCC (I/II/III/IVa = 7/7/14/3) were enrolled in this study. One course of treatment consisted of protracted venous infusions (PVIs) of 5-FU (400 mg/m2/24 hours for days 1-5 and 8-12), CDDP (40 mg/m2/3 hours on days 1 and 8) and radiation (2 Gy/d on days 1-5, 8-12, and 15-19), and a 2nd course was successively repeated after a 2-week interval. A total of 8 measurements of the plasma concentration of 5-FU were made using high performance liquid chromatography. Genetic polymorphisms examined herein included those in the genes coding thymidylate synthase (TS), glutathione S-transferase P1 (GSTP1), multidrug resistant transporter MDR1/P-glycoprotein, and intercellular adhesion molecule-1, and in a circadian rhythm-relating gene, CLOCK.

RESULTS:

The CR rate depended on stage (P = 0.001), but the analysis was not sufficiently powered to reach a level of statistical significance for the 2-year survival rate (P = 0.061). For stage II/III patients, to have 2 or 3 polymorphisms of 3R/3R of 5'-TSER, a 6 bp of 3'-TSUTR, and GSTP1-Ile105Val resulted in an extensively longer survival (P = 0.020), although no difference was found between 2 groups, with respect to the plasma concentrations of 5-FU and clinicopathologic characteristics.

CONCLUSIONS:

The prognostic index may allow predictions of the clinical outcome of a 5-FU/CDDP-based CRT in stage II/III ESCC patients.

• Authors: Tatsuya Okuno, Takao Tamura, Motohiro Yamamori, Naoko Chayahara, Toshio Yamada, Ikuya Miki, Noboru Okamura, Yuko Kadowaki, Daisuke Shirasaka, Nobuo Aoyama, Tsutomu Nakamura, Katsuhiko Okumura, Takeshi Azuma, Masato Kasuga, Toshiyuki Sakaeda
• Journal: American journal of clinical oncology (Am J Clin Oncol) Vol. 30 Issue 3 Pg. 252-7 (Jun 2007) ISSN: 1537-453X [Electronic] United States
• PMID: 17551301 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cisplatin
• Fluorouracil

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Asian People (genetics)
• Carcinoma, Squamous Cell (genetics, therapy)
• Cisplatin (administration & dosage)
• Combined Modality Therapy
• Esophageal Neoplasms (genetics, therapy)
• Female
• Fluorouracil (administration & dosage)
• Humans
• Male
• Middle Aged
• Polymorphism, Genetic
• Prognosis
• Radiotherapy