624P - Weekly versus biweekly combination of docetaxel (D)-cisplatin (C)-5FU (F) in advanced gastric cancer and esogastric junction adenocarcinoma (aGC):...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Oesophageal Cancer
Gastric Cancer
Presenter Amélie Deleporte
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors A. Deleporte1, M. van den Eynde2, F. Forget3, S. Holbrechts4, T. Delaunoit5, G. Houbiers6, H. Rezaei Kalantari7, S. Laurent8, E. Vanderstraeten9, M. De Man10, P. Vergauwe11, M. Clausse12, J. Vanderauwera13, P. Pierre14, L. D'Hondt15, B. Ghillemijn16, A. Covas1, M. Paesmans17, L. Ameye17, A. Hendlisz1
  • 1Medical Oncology, Institut Jules Bordet, 1000 - Brussels/BE
  • 2Medical Oncology, Cliniques universitaires St-Luc, 1200 - Brussels/BE
  • 3Oncology, Centre hospitalier de l'Ardenne, Libramont/BE
  • 4Medical Oncology, Hopital Ambroise Pare, Mons/BE
  • 5Gastroenterology, Entité Jolimontoise, La Louviere/BE
  • 6Gastroenterology, Hopital Saint Joseph, Liege/BE
  • 7Medical Oncology & Hematology, Centre Hospitalier Peltzer La Tourelle (CHPLT), 4800 - Verviers/BE
  • 8Gastro-enterologie, UZ Gent, 9000 - Gent/BE
  • 9Medical Oncology, Maria Middelares Hospital, gent/BE
  • 10Medical Oncology, Aalst OLV-Ziekenhuis, Aalst/BE
  • 11Gastroenterology, A.Z. Groeninge, 8500 - Kortrijk/BE
  • 12Internal Medicine, Clinique St.-Luc Bouge, Bouge/BE
  • 13Medical Oncology, AZ Monica Florent Pauwels, Deurne/BE
  • 14Medical Oncology, Clinique du Sud-Luxembourg (Arlon), Arlon/BE
  • 15Medical Oncology, CHU Dinant Godinne, 5530 - Yvoir/BE
  • 16Medical Oncology, AZ Ronse, Ronse/BE
  • 17Data Centre, Institute Jules Bordet, BE-1000 - Brussels/BE

Abstract

Aim

Triweekly DCF is a standard treatment in aGC, but is, however, associated with a bleak 30% febrile neutropenia (FN) incidence requiring prophylactic administration of granulocyte-colony stimulating factor (G-CSF). The DoGE study aims to define efficient but less toxic alternate DCF combinations.

Methods

Chemonaive patients (pts) with aGC, age ≥ 18, PS ≤1 and normal organ function were randomized in a multicentric phase II trial (EudraCT 2008-000551-10) between a weekly (D 40 mg/m2,C 35 mg/m2, folinic Acid (FA) 400 mg/m2, F 1800 mg/m2 24 h infusion on days 1 and 8 every 3 weeks (wks), arm 1) and a biweekly regimen (D 50 mg/m2, C 50 mg/m2, FA 400 mg/m2, F 2000 mg/m2 48 h infusion every 2 wks, arm 2). G-CSF was allowed only as secondary prevention. The tumors were assessed every 6 wks. A Briant & Day two -teps design with toxicity and rate of non-progressive disease as primary endpoints was used. Insufficient efficacy was defined as 6 wks-disease control rate (DCR) < 70% and excessive toxicity as >25% FN (ß = 10% and α = 10% for activity, 15% for toxicity).

Results

Between Oct 2008 and Oct 2013, 106 pts were recruited in 15 centers: 76 males (71.7%), PS 0/1: 60 (57%)/46 (43%), median age 62(33-85). Early study closure due to slow accrual led to a reduced 80% power. Among the 103 pts who received the study medications (52 arm 1 and 51 arm 2), 77% and 86% experienced grade III-IV toxic reactions, mainly neutropenia (21%,95% CI 12-34 in arm 1 vs 59%, 95% CI 45-71 in arm 2), and similar fatigue (27% vs 25%), anorexia (19% vs 18%) and diarrhea (15% vs 12%) in both arms. The 6 wks-DCR was 83%, 95% CI 71-91 in arm 1 and 79%, 95% CI 67-88 in arm 2. The pts' outcomes are reported hereunder.

Regimen Grade III-IV toxicities* FN at 6 wks* Toxic deaths* mOS mPFS
Weekly (arm1) 77 (64-86) 9.6 (4-21) 9 (4-20) 8.2 (6.0-14.5) 5.1 (3.2-6.5)
Biweekly (arm2) 86 (74-93) 6 (2-16) 4 (1-13) 11.9 (7.4-15.9) 5.2 (3.0-6.9)

* in % (95% CI); ¶ in months (95% CI)

Conclusions

Weekly and biweekly DCF meet the study's safety requirements with less than 10% FN rate without G-CSF support. Both regimens have adequate efficacy according to the study design, consistent with the literature findings on the triweekly regimen, and represent valuable alternatives for further clinical development.

Disclosure

All authors have declared no conflicts of interest.