Randomized multicenter phase III study of a modified docetaxel and cisplatin plus fluorouracil regimen compared with cisplatin and fluorouracil as first-line therapy for advanced or locally recurrent gastric cancer

Abstract

Background: The V325 study showed that docetaxel, cisplatin, and fluorouracil (DCF) prolonged overall survival (OS) of patients with advanced gastric cancer, but with a high incidence of dose-limiting toxicities. We investigated the efficacy and safety of a modified DCF (mDCF) regimen for Chinese patients with advanced gastric cancer.

Methods: Untreated advanced gastric cancer patients randomly received docetaxel and cisplatin at 60 mg/m(2) (day 1) followed by fluorouracil at 600 mg/m(2)/day (days 1-5; mDCF regimen) or cisplatin at 75 mg/m(2) (day 1) followed by fluorouracil at 600 mg/m(2)/day (days 1-5; CF) every 3 weeks. The primary end point was progression-free survival (PFS). The secondary end points were OS, overall response rate (ORR), time-to-treatment failure (TTF), and safety.

Results: In total, 243 patients were randomized to treatment (mDCF regimen 121; CF 122). Compared with CF, the mDCF regimen significantly improved PFS and OS: the median PFS was 7.2 and 4.9 months, respectively [hazard ratio (HR) 0.58, log-rank P = 0.0008], and the median OS was 10.2 and 8.5 months, respectively (HR = 0.71, P = 0.0319). Additionally, the mDCF regimen improved the parameters used as secondary objectives: the ORR was 48.7% with the mDCF regimen versus 33.9% with CF (P = 0.0244); the median TTF was 3.4 months with the mDCF regimen and 2.4 months with CF (HR = 0.67, P = 0.0027). Grade 3 and grade 4 treatment-related adverse events occurred in 77.3 % of patients who received the mDCF regimen versus 46.1% of patients who received CF (P < 0.001).

Conclusions: The mDCF regimen, compared with CF, significantly prolonged PFS and OS and enhanced ORR of Chinese patients with advanced gastric cancer. The mDCF regimen achieved efficacy comparable to that of DCF but with fewer toxicities, which is appropriate for the Chinese population.

Keywords: Advanced gastric cancer; Modified docetaxel and cisplatin plus fluorouracil regimen; Overall survival; Progression-free survival; Safety.

Fig. 1

The Consolidated Standards of Reporting Trials (CONSORT) diagram depicting the trajectory of the trial. AJCC American Joint Committee on Cancer, ALT alanine transaminase, AST aspartate transaminase, CF cisplatin and fluorouracil, mDCF modified docetaxel, cisplatin, and 5-fluorouracil regimen, UNL upper normal limit

Fig. 2

a The Kaplan–Meier distribution of progression-free survival (PFS). Patients with advanced gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction were randomly assigned to receive docetaxel, cisplatin, and 5-fluorouracil (DCF) or cisplatin and 5-fluorouracil (CF). b PFS [hazard ratios (HR) and 95 % confidence intervals (CI)] for selected subgroup analyses. c The Kaplan–Meier distribution of overall survival (OS). KPS Karnofsky performance status, LCL lower confidence limit, UCL upper confidence limit

Fig. 3

a The Kaplan–Meier distribution of overall response duration. Patients with advanced gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction were randomly assigned to receive docetaxel, cisplatin, and 5-fluorouracil (DCF) or cisplatin and 5-fluorouracil (CF). Duration of response was calculated in responders and was defined from the onset of partial response/complete response. b The Kaplan–Meier distribution of the time to treatment failure