Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: a randomized placebo-controlled phase III study.
OBJECTIVE
Clinical trials demonstrated the efficacy and safety of intravenous (i.v.) or subcutaneous (s.c.) amifostine for reducing xerostomia and mucositis after radiotherapy or radiochemotherapy for head-and-neck cancer. This randomized, double-blinded, placebo-controlled, phase III study evaluated the efficacy and safety of i.v. amifostine during radiochemotherapy for head-and-neck cancer.


METHODS
Patients from European and American study centers received i.v. amifostine 300 mg/m2 (n = 67) or placebo (n = 65) before carboplatin 70 mg/m2 and radiotherapy on Days 1 to 5 and 21 to 25, and i.v. amifostine 200 mg/m2 or placebo before radiotherapy on other days.


RESULTS
Toxicity incidences were (amifostine, placebo, p value): Grade 2 or higher acute xerostomia (39%, 34%, 0.715), Grade 3 or higher acute mucositis (39%, 22%, 0.055), Grade 2 or higher late xerostomia (37%, 24%, 0.235), and Grade 3 or higher treatment-related adverse events (42%, 20%, 0.008). One-year rates of locoregional failure, progression-free survival, and overall survival were not significantly different between treatments.


CONCLUSIONS
The used amifostine doses were not able to reduce the toxicity of simultaneous radiochemotherapy for head-and-neck cancer. The safety of amifostine and the lack of tumor protection were consistent with previous studies.
Buentzel
Jens
J
Department of Otolaryngology, Head & Neck Surgery, Suedharzkrankenhaus Nodhausen, Nordhausen, Germany. jens.buentzel@shk-ndh.de
Micke
Oliver
O
Adamietz
Irenaus A
IA
Monnier
Alain
A
Glatzel
Michael
M
de Vries
Alexander
A
D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects; D016190:Carboplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D013280:Stomatitis / Q000209:etiology / Q000517:prevention & control*; D015996:Survival Rate; D014987:Xerostomia / Q000209:etiology / Q000517:prevention & control*
D000970:Antineoplastic Agents; D011837:Radiation-Protective Agents; D016190:Carboplatin; D004999:Amifostine