Fortnightly or fractionated weekly docetaxel-cisplatin-5-FU as first-line treatment in advanced gastric and gastroesophageal junction adenocarcinoma: The randomized phase II DoGE study

Cancer Med. 2021 Jul;10(13):4366-4374. doi: 10.1002/cam4.3976. Epub 2021 May 31.

Abstract

Background: While docetaxel/cisplatin/5-fluorouracil (DCF) outperforms CF in first-line gastric adenocarcinoma, toxicity remains an issue.

Methods: This multicenter phase II trial randomized chemonaïve metastatic gastric adenocarcinoma patients to fractionated weekly DCF (D 40 mg/m2 , C 35 mg/m², F 1800 mg/m² over 24 h, on days 1 and 8 every 3 weeks, arm (1) or fortnightly DCF (D 50 mg/m2 , C 50 mg/m², F 2000 mg/m² over 48 h every 2 weeks, arm (2). Prophylactic granulocyte colony-stimulating factor (G-CSF) was not allowed. The primary endpoint was the rate of febrile neutropenia within the first six treatment weeks (early FN).

Results: A total of 106 eligible patients were recruited. The early and overall FN rates were 9.5% and 17% in arm 1, respectively, and 5.9% and 8% in arm 2, respectively. Grade ≥3 toxicities occurred in 81% of patients in arm 1 and 90% of patients in arm 2, the most common being neutropenia (33% vs. 61%), fatigue (27% vs. 25%), vomiting (21% vs. 12%), anorexia (19% vs. 18%), and diarrhea (17% vs. 10%). Median progression-free survival and overall survival were 5.1 (95% CI, 3.2-6.5) and 8.2 months (95% CI, 6.0-14.5), respectively, in arm 1 and 5.2 (95% CI, 3.0-6.9) and 11.9 months (95% CI, 7.4-15.9), respectively, in arm 2.

Conclusions: Fractionated weekly and fortnightly DCF regimens are associated with a low risk of early FN, and a better hematological toxicity profile as compared to historical DCF without compromising efficacy. Both regimens offer greater convenience removing the need for systematic use of prophylactic G-CSF.

Keywords: 5-FU; cisplatin; docetaxel; fortnightly; gastric cancer; gastroesophageal cancer; hematological growth factors; weekly.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Anorexia / chemically induced
  • Anorexia / epidemiology
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Diarrhea / chemically induced
  • Diarrhea / epidemiology
  • Docetaxel / administration & dosage
  • Docetaxel / adverse effects
  • Drug Administration Schedule
  • Esophagogastric Junction*
  • Fatigue / chemically induced
  • Fatigue / epidemiology
  • Febrile Neutropenia / epidemiology
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Granulocyte Colony-Stimulating Factor
  • Humans
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Neutropenia / epidemiology
  • Progression-Free Survival
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Vomiting / chemically induced
  • Vomiting / epidemiology

Substances

  • Granulocyte Colony-Stimulating Factor
  • Docetaxel
  • Cisplatin
  • Fluorouracil

Grants and funding