PHASE II-III RANDOMISED TRIAL OF DEFINITIVE CHEMORADIOTHERAPY WITH FOLFOX OR CISPLATIN AND FLUOROURACIL IN ESOPHAGEAL CANCER PRODIGE 5 - ACCORD 17 trial: final results T. Conroy, MP. Galais, JL. Raoul, O. Bouché, S. Gourgou, JY. Douillard, PL. Etienne, V. Boige, I. Martel-Lafay, P. Michel, C. Llacer-Moscardo, J. Bérille, L. Bedenne, A. Adenis; UNICANCER-GI/PRODIGE Group Centre Alexis Vautrin, Nancy; Centre François Baclesse, Caen; Centre Eugène Marquis, Rennes and Institut Paoli-Calmettes, Marseille; Centre Hospitalier R. Debré, Reims; Centre Val d’Aurelle, Montpellier; Institut de Cancérologie de l’Ouest, Nantes; Clinique Armoricaine, Saint Brieuc; Institut Gustave Roussy, Villejuif; Centre Léon Bérard, Lyon; Centre Hospitalier Universitaire, Rouen; UNICANCER R&D, Paris; Centre Hospitalier Universitaire, Dijon; Centre Oscar Lambret, Lille; FRANCE
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PHASE II-III RANDOMISED TRIAL OF DEFINITIVE
CHEMORADIOTHERAPY WITH FOLFOX OR CISPLATIN
AND FLUOROURACIL IN ESOPHAGEAL CANCER
PRODIGE 5 - ACCORD 17 trial: final results
T. Conroy, MP. Galais, JL. Raoul, O. Bouché, S. Gourgou,
JY. Douillard, PL. Etienne, V. Boige, I. Martel-Lafay, P. Michel,
C. Llacer-Moscardo, J. Bérille, L. Bedenne, A. Adenis; UNICANCER-GI/PRODIGE Group
Centre Alexis Vautrin, Nancy; Centre François Baclesse, Caen; Centre Eugène Marquis, Rennes and
Institut Paoli-Calmettes, Marseille; Centre Hospitalier R. Debré, Reims; Centre Val d’Aurelle,
Montpellier; Institut de Cancérologie de l’Ouest, Nantes; Clinique Armoricaine, Saint Brieuc;
Institut Gustave Roussy, Villejuif; Centre Léon Bérard, Lyon; Centre Hospitalier Universitaire, Rouen;
UNICANCER R&D, Paris; Centre Hospitalier Universitaire, Dijon; Centre Oscar Lambret, Lille; FRANCE
Background
Concurrent chemoradiation using 5FU-Cisplatin is the
standard of care in unresectable localized esophageal
cancer.
With 5FU-cisplatin based chemoradiation (RTOG 85-01):
20% of patients experienced major toxicities
Local failure rate was 45%
Herskovic A et al., N Engl J Med 1992;326:1593-8.
In a randomized phase II study in 97 patients comparing Folfox to
5FU-Cisplatin, definitive chemoradiotherapy with Folfox provided
a high CR rate with a favorable toxicity profile
Conroy T et al., Br J Cancer 2010;103:1349-55.
The study has been extended into a phase III trial
Prodige 5 - ACCORD 17 trial design
Stratification :
adenocarcinoma vs squamous-cell vs adenosquamous
pretreatment weight loss < 10% vs ≥ 10%
performance status: 0 vs 1 vs 2
center
Unresectable
esophageal
cancer
R
A
N
D
O
M
I
Z
E
50 Gy/5 weeks
+ Folfox, 3 cycles
50 Gy/5 weeks +
5FU/cisplatin, 2 cy.
Folfox,
3 cycles
5FU/cisplatin,
2 cycles
Arm A: Folfox + RT 50 Gy
Chemotherapy in Folfox arm: six bi-monthly cycles of FOLFOX, the first 3 cycles starting
on D1, D15 and D29 concomitant with 5 weeks’ radiotherapy.
Modified Folfox:
On day 1, Oxaliplatin 85mg/m², leucovorin 200mg/m², 5-FU bolus 400mg/m²/d
and from day 1 to 2, 5-FU continuous infusion 800 mg/m²/day.
Tumor assessment on week 15
Cycle 3
CRT RT
d3-5 d8-12
RT
CT CT CT
d29-30 d31-33 d22-26
RT CRT RT
d17-19 d15-16
Cycle 2
Wk 7 Wk 9 Wk 11
Wk 1 Wk 3 Wk 2
d43-44
Cycle 4
d57-58
Cycle 5
d71-72
Cycle 6
d1-2
Cycle 1
CRT RT
Wk 3 Wk 5
Chemotherapy in 5FU-Cisplatin arm: two cycles of 5-FU/Cisplatin on week 1 and 5 of
radiotherapy and two cycles of chemotherapy with 5-FU/Cisplatin on weeks 8 and 11;
5FU-cisplatin regimen:
On D1, Cisplatin 75 mg/m² with hydration and from day 1 to 4, 5-FU 1000 mg/m²/day.
Tumor assessment on week 15
Herskovic A et al., N Engl J Med 1992;326:1593-8.
Arm B: 5FU-cisplatin + RT 50 Gy
Wk 1
CT
d50-53
Cycle 3
CRT
d29-32 d33
Cycle 2
d22-26
RT RT
d15-19
CRT
d1-4 d5 d8-12
RT
Cycle 1
RT RT
Wk 3 Wk 5 Wk 2 Wk 4
CT
d71-74
Cycle 4
Wk 11 Wk 7
Main Inclusion Criteria
Patients unfit for surgery or locally advanced esophageal
carcinoma (disease status: any T, N0 or N1, M0 or M1a)