Hyperfractionated accelerated chemoradiation with concurrent fluorouracil-mitomycin is more effective than dose-escalated hyperfractionated accelerated radiation therapy alone in locally advanced head and neck cancer: final results of the radiotherapy cooperative clinical trials group of the German Cancer Society 95-06 Prospective Randomized Trial.
OBJECTIVE
To report the results and corresponding acute and late reactions of a prospective, randomized, clinical study in locally advanced head and neck cancer comparing concurrent fluorouracil (FU) and mitomycin (MMC) chemotherapy and hyperfractionated accelerated radiation therapy (C-HART; 70.6 Gy) to hyperfractionated accelerated radiation therapy alone (HART; 77.6 Gy).


METHODS
Three hundred eighty-four stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer patients were randomly assigned to receive either 30 Gy (2 Gy every day) followed by 1.4 Gy bid to a total of 70.6 Gy concurrently with FU (600 mg/m(2), 120 hours continuous infusion) days 1 through 5 and MMC (10 mg/m(2)) on days 5 and 36 (C-HART) or 14 Gy (2 Gy every day) followed by 1.4 Gy bid to a total dose of 77.6 Gy (HART). The data were analyzed on an intent-to-treat basis.


RESULTS
At 5 years, the locoregional control and overall survival rates were 49.9% and 28.6% for C-HART versus 37.4% and 23.7% for HART, respectively (P = .001 and P = .023, respectively). Progression-free and freedom from metastases rates were 29.3% and 51.9% for C-HART versus 26.6% and 54.7% for HART, respectively (P = .009 and P = .575, respectively). For C-HART, maximum acute reactions of mucositis, moist desquamation, and erythema were lower than with HART, whereas no differences in late reactions and overall rates of secondary neoplasms were observed.


CONCLUSIONS
C-HART (70.6 Gy) is superior to dose-escalated HART (77.6 Gy) with comparable or less acute reactions and equivalent late reactions, indicating an improvement of the therapeutic ratio.
Budach
Volker
V
Department of Radiation Oncology, University Hospitals Charité, Berlin, Germany. volker.budach@charite.de
Stuschke
Martin
M
Budach
Wilfried
W
Baumann
Michael
M
Geismar
Dirk
D
Grabenbauer
Gerhard
G
Lammert
Ingrid
I
Jahnke
Klaus
K
Stueben
Georg
G
Herrmann
Thomas
T
Bamberg
Michael
M
Wust
Peter
P
Hinkelbein
Wolfgang
W
Wernecke
Klaus-Dieter
KD
D000206:Actuarial Analysis; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005858:Germany; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D010349:Patient Compliance; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D016019:Survival Analysis; D015996:Survival Rate
D016685:Mitomycin; D005472:Fluorouracil