Details

Autor(en) / Beteiligte

• Jeong, Jae Ho
• Park, Sook Ryun
• Ahn, Yongchel
• Ryu, Min-Hee
• Ryoo, Baek-Yeol
• Kong, Sun-Young
• Yook, Jeong Hwan
• Yoo, Moon-Won
• Kim, Beom Su
• Kim, Byung Sik
• Kang, Yoon-Koo

Titel

Associations between CYP2A6 polymorphisms and outcomes of adjuvant S-1 chemotherapy in patients with curatively resected gastric cancer

Ist Teil von

• Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2017, Vol.20 (1), p.146-155

Ort / Verlag

Tokyo: Springer Japan

Erscheinungsjahr

2017

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• Background Oral fluoropyrimidine S-1 contains tegafur, which is metabolized to 5-fluorouracil by cytochrome P450 2A6 (CYP2A6). We here examined associations between CYP2A6 polymorphisms and treatment outcomes of adjuvant S-1 in gastric cancer patients. Methods Patients received adjuvant S-1 (40 mg/m 2 twice daily, days 1–28, every 6 weeks for eight cycles) after curative surgery for pathological stage II–III gastric cancer. We analyzed the wild-type allele (W) ( CYP2A6*1 ) and four variant alleles (V) ( CYP2A6*4 , *7 , *9 , *10 ) that abolish or reduce this enzyme activity. Results Patients ( n  = 200) were enrolled between November 2007 and July 2013 with the following clinical characteristics: median age, 57 years (range, 32–83 years); 128 men, 72 women. With a median follow-up of 46.4 months, the 3-year relapse-free survival (RFS) and overall survival (OS) rates were 83.1 % (95 % CI, 77.7–88.5 %) and 94.8 % (95 % CI, 91.6–98.0 %), respectively. Genotype distributions were as follows: W/W ( n  = 49, 24.5 %), W/V ( n  = 94, 47.0 %), and V/V ( n  = 57, 28.5 %). Overall toxicity did not differ according to genotype for any grade ( p  = 0.612) or grade ≥3 ( p  = 0.143). However, RFS differed significantly according to CYP2A6 genotype. The 3-year RFS rates were 95.9 % for W/W , 83.1 % for W/V , and 72.5 % for V/V ( p  = 0.032). Carriers of W/V and V/V genotypes had a poorer RFS with a hazard ratio of 3.41 (95 % CI, 1.01–11.52; p  = 0.049) and 4.03 (95 % CI, 1.16–13.93; p  = 0.028), respectively, compared with the W/W genotype. Conclusions CYP2A6 polymorphisms are not associated with toxicity of S-1 chemotherapy, but correlate with the efficacy of S-1 in the adjuvant setting for gastric cancer.