[Concomitant bifractionated radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in locally progressive, non-resectable epidermoid carcinomas of the pharynx: ten years experience at the Antoine Lacassagne center].
OBJECTIVE
Patients suffering from locally advanced unresectable squamous cell carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have a poor prognosis. More than 70% of patients die within 5 years mainly due to local recurrences. The aim of this study was to evaluate retrospectively the Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity, the response rates, the survival, and the clinical prognostic factors.


METHODS
From 1992 to 2000, 92 consecutive patients were treated in our single institution. All of them had stage IV, unresectable squamous cell carcinoma of the pharynx and they received continuous bid radiotherapy (two daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5-fluorouracil (5FU) were given during radiotherapy at 21-day intervals (third not delivered after the end of the radiotherapy). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (750 mg/m2/day at 1st course; 430 mg/m2/day at 2nd and 3rd courses). Special attention was paid to supportive care, particularly in terms of enteral nutrition and mucositis prevention by low-level laser energy.


RESULTS
Acute toxicity was marked and included WHO grade III/IV mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and grade III/IV neutropenia (61%). This toxicity was significant but manageable with optimised supportive care, and never led to interruption of treatment for more than 1 week, although there were two toxic deaths. Complete global response rate at 6 months was 74%. Overall global survival at 1 and 2 years was 72% and 50% respectively, with a median follow-up of 17 months. Prognostic factors for overall survival were the Karnofsky index (71% survival at 3 years for patients with a Karnofsky index of 90-100% versus 30% for patients with a Karnofsky index of 80% versus 0% for patients with a Karnofsky index of 60-70%, p = 0.0001) and tumor location (55% at 3 years for oropharynx versus 37% for panpharynx versus 28% for hypopharynx, p = 0.009).


CONCLUSIONS
These results confirm the efficacy of concomitant bid radiotherapy and chemotherapy in advanced unresectable tumor of the pharynx. The improvement in results will essentially depend on our capacity to restore in a good nutritional status the patients before beginning this heavy treatment.
Magné
N
N
Centre Antoine-Lacassagne, 33, avenue de Valombrose, 06189 Nice, France.
Pivot
X
X
Marcy
P Y
PY
Chauvel
P
P
Courdi
A
A
Dassonville
O
O
Poissonnet
G
G
Vallicioni
J
J
Ettore
F
F
Falewee
M N
MN
Milano
G
G
Santini
J
J
Lagrange
J L
JL
Schneider
M
M
Demard
F
F
Bensadoun
R J
RJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004750:Enteral Nutrition; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000000981:diagnostic imaging; D010610:Pharyngeal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D011379:Prognosis; D016016:Proportional Hazards Models; D011855:Radiodermatitis / Q000209:etiology; D011877:Radionuclide Imaging; D013280:Stomatitis / Q000139:chemically induced / Q000517:prevention & control; D016019:Survival Analysis; D016896:Treatment Outcome
D002945:Cisplatin; D005472:Fluorouracil
Radiothérapie bifractionnée et chimiothérapie par cisplatine et 5-fluoro-uracile concomitantes dans les carcinomes épidermoïdes localement évolués non résécables du pharynx: dix ans d'expérience au centre Antoine Lacassagne.