French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC).
BACKGROUND
Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002.


METHODS
Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1-->D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m2 (D1, D22, D43); 5FU, continuous infusion (D1-->D5), 750 mg/m2/day cycle 1; 430 mg/m2/day cycles 2 and 3.


RESULTS
A total of 163 evaluable patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p = 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years.


CONCLUSIONS
For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an "aggressive" dose-intensity radiotherapy schedule.
Bensadoun
René-Jean
RJ
Department of Radiation Oncology, Centre Antoine Lacassagne, Nice, France. rene-jean.bensadoun@nice.fnclcc.fr
Bénézery
Karen
K
Dassonville
Olivier
O
Magné
Nicolas
N
Poissonnet
Gilles
G
Ramaïoli
Alain
A
Lemanski
Claire
C
Bourdin
Sylvain
S
Tortochaux
Jacques
J
Peyrade
Frédéric
F
Marcy
Pierre-Yves
PY
Chamorey
Emmanuel
E
Vallicioni
Jacques
J
Seng
Hang
H
Alzieu
Claude
C
Géry
Bernard
B
Chauvel
Pierre
P
Schneider
Maurice
M
Santini
José
J
Demard
François
F
Calais
Gilles
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005602:France; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D008297:Male; D008875:Middle Aged; D037981:Neck Dissection; D009364:Neoplasm Recurrence, Local; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D010610:Pharyngeal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D011446:Prospective Studies; D016019:Survival Analysis
D002945:Cisplatin; D005472:Fluorouracil