Department of Internal Medicine, Seoul National University Hospital, 101 Daehang-Ro, Jongno-Gu, Seoul, Korea.
Cancer Chemother Pharmacol. 2011 Jun;67(6):1323-31. doi: 10.1007/s00280-010-1425-7. Epub 2010 Aug 24.
To evaluate the efficacy and safety of S-1 in combination with oxaliplatin in a biweekly schedule as first-line treatment in metastatic colorectal cancer and the association between genetic polymorphisms and treatment outcomes.
Eligibility included age 18-75 years, at least one measurable lesion, no prior chemotherapy except adjuvant chemotherapy, and Eastern Cooperative Oncology Group Performance Status (PS) 0-2. S-1 40 mg/m(2) b.i.d. on days 1-7 with 85 mg/m(2) of oxaliplatin on day 1 was repeated every 2 weeks. Genomic DNA from whole blood was analyzed for 15 single-nucleotide polymorphisms (SNPs) among 8 genes.
Fifty-two patients (median age 63 years, range 37-74) were enrolled: 37 men and 15 women; 44 with a PS of 0 and 8 with a PS of 1; and 41 with initially metastatic cancer and 11 with relapsed disease. Among 51 evaluable patients, objective response rate was 47.1% [95% confidence interval (CI) 32.9-61.2]. Median follow-up duration was 17.1 months (range 3.9-28.2 months). Median progression-free survival (PFS) was 6.4 months (95% CI 4.8-8.1), and median overall survival had not been reached yet. Reported grade 3 toxicities were neutropenia (7.7%), thrombocytopenia (5.8%), sensory neuropathy (7.7%) and diarrhea (1.9%). There was no grade 4 toxicity or neutropenic fever. Patients with A/G or G/G genotype in GSTP1 Ile105Val SNP had longer PFS than patients with A/A (median 8.3 vs. 6.1 months, P = 0.04).
Biweekly S-1 with oxaliplatin is effective and has improved tolerability and convenience compared to other fluoropyrimidine with oxaliplatin combinations. GSTP1 Ile105Val SNP is associated with treatment outcomes.
评估 S-1 联合奥沙利铂双周方案作为转移性结直肠癌一线治疗的疗效和安全性，以及遗传多态性与治疗结果之间的关系。
纳入标准为年龄 18-75 岁，至少有一处可测量病灶，除辅助化疗外无既往化疗史，东部肿瘤协作组体力状况（PS）0-2 分。S-1 40 mg/m2，bid，第 1-7 天，奥沙利铂 85 mg/m2，第 1 天，每 2 周重复。从全血基因组 DNA 中分析 8 个基因中的 15 个单核苷酸多态性（SNP）。
52 例患者（中位年龄 63 岁，范围 37-74 岁）入组：男 37 例，女 15 例；PS 0 级 44 例，PS 1 级 8 例；初诊转移性癌症 41 例，复发疾病 11 例。在 51 例可评估患者中，客观缓解率为 47.1%[95%可信区间（CI）32.9-61.2]。中位随访时间为 17.1 个月（范围 3.9-28.2 个月）。中位无进展生存期（PFS）为 6.4 个月（95%CI 4.8-8.1），中位总生存期尚未达到。报告的 3 级毒性为中性粒细胞减少（7.7%）、血小板减少（5.8%）、感觉神经病变（7.7%）和腹泻（1.9%）。无 4 级毒性或中性粒细胞减少性发热。GSTP1 Ile105Val SNP 中 A/G 或 G/G 基因型患者的 PFS 长于 A/A 基因型患者（中位 8.3 个月比 6.1 个月，P=0.04）。
与其他氟嘧啶联合奥沙利铂方案相比，S-1 联合奥沙利铂双周方案治疗转移性结直肠癌有效，且耐受性和便利性更好。GSTP1 Ile105Val SNP 与治疗结果相关。
