J Clin Oncol. 2015 Nov 20;33(33):3874-9. doi: 10.1200/JCO.2015.60.7465.
Docetaxel, cisplatin, and fluorouracil (DCF) is a standard first-line three-drug chemotherapy regimen for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma and is associated with significant toxicity. We examined the safety and efficacy of a modified DCF (mDCF) regimen in a randomized multicenter phase II study.
Previously untreated patients with metastatic gastric or GEJ adenocarcinoma were randomly assigned to receive either mDCF (fluorouracil 2,000 mg/m2 intravenously [IV] over 48 hours, docetaxel 40 mg/m2 IV on day 1, cisplatin 40 mg/m2 IV on day 3, every 2 weeks) or parent DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, and fluorouracil 750 mg/m2 IV over 5 days with granulocyte colony-stimulating factor, every 3 weeks). The study had 90% power to differentiate between 6-month progression-free survival of 26% and 43%, with type I and II error rates of 10% each. An early stopping rule for toxicity was included, defined as grade 3 to 4 adverse event rate > 70% in the first 3 months.
From November 2006 to June 2010, 85 evaluable patients were enrolled (male, n = 61; female, n = 24; median age, 58 years; Karnofsky performance status, 90%; GEJ, n = 28; gastric, 57). mDCF (n = 54) toxicity rates included 54% grade 3 to 4 toxicity (22% hospitalized) within the first 3 months and 76% grade 3 to 4 toxicity over the course of treatment. The DCF arm (n = 31) closed early because of toxicity, with rates of 71% grade 3 to 4 toxicity (52% hospitalized) within 3 months and 90% grade 3 to 4 toxicity over the course of treatment. Six-month PFS was 63% (95% CI, 48% to 75%) for mDCF and 53% (95% CI, 34% to 69%) for DCF. Median overall survival was improved for mDCF (18.8 v 12.6 months; P = .007).
mDCF is less toxic than parent DCF, even when supported with growth factors, and is associated with improved efficacy. mDCF should be considered a standard first-line option for patients with metastatic gastric or GEJ adenocarcinoma.
多西紫杉醇、顺铂和氟尿嘧啶（DCF）是晚期胃或胃食管交界处（GEJ）腺癌的标准一线三药化疗方案，具有显著的毒性。我们在一项随机多中心 II 期研究中检查了改良 DCF（mDCF）方案的安全性和疗效。
既往未经治疗的转移性胃或 GEJ 腺癌患者被随机分配接受 mDCF（氟尿嘧啶 2000mg/m2 静脉滴注 48 小时，多西紫杉醇 40mg/m2 静脉滴注第 1 天，顺铂 40mg/m2 静脉滴注第 3 天，每 2 周 1 次）或亲本 DCF（多西紫杉醇 75mg/m2、顺铂 75mg/m2、氟尿嘧啶 750mg/m2 静脉滴注 5 天，并用粒细胞集落刺激因子，每 3 周 1 次）。该研究有 90%的效能来区分 6 个月无进展生存率为 26%和 43%，I 型和 II 型错误率分别为 10%。包括毒性的早期停止规则，定义为前 3 个月中 3 级至 4 级不良事件发生率>70%。
从 2006 年 11 月至 2010 年 6 月，共纳入 85 例可评估患者（男性，n=61；女性，n=24；中位年龄 58 岁；卡诺夫斯基表现状态，90%；GEJ，n=28；胃，57）。mDCF（n=54）的毒性发生率包括前 3 个月内 54%的 3 级至 4 级毒性（22%住院）和治疗过程中 76%的 3 级至 4 级毒性。DCF 组（n=31）因毒性而提前关闭，前 3 个月内有 71%的 3 级至 4 级毒性（52%住院），治疗过程中 90%的 3 级至 4 级毒性。mDCF 的 6 个月 PFS 为 63%（95%CI，48%至 75%），而 DCF 为 53%（95%CI，34%至 69%）。mDCF 的中位总生存期有所改善（18.8 个月 vs 12.6 个月；P=0.007）。
mDCF 比亲本 DCF 的毒性更小，即使支持生长因子也是如此，并且与疗效的提高相关。mDCF 应被视为转移性胃或 GEJ 腺癌患者的标准一线选择。
