Subcutaneous compared with intravenous administration of amifostine in patients with head and neck cancer receiving radiotherapy: final results of the GORTEC2000-02 phase III randomized trial.
OBJECTIVE
To compare compliance with and efficacy of intravenous (IV) and subcutaneous (SC) amifostine for the treatment of patients undergoing radiotherapy for head and neck cancer.


METHODS
Patients with newly diagnosed squamous cell carcinoma of the head and neck, who were eligible for radiotherapy and who were not receiving concurrent chemotherapy, were randomly assigned to receive either IV amifostine (200 mg/m(2) daily for 3 minutes, 15 to 30 minutes before irradiation) or SC amifostine (500 mg; two sites; 20 to 60 minutes before irradiation). The primary end point was late xerostomia at 1 year as indicated by unstimulated and stimulated salivary flow rates, a patient benefit questionnaire score, and Radiation Therapy Oncology Group (RTOG) late toxicity grade.


RESULTS
Results for IV (n = 143) versus SC (n = 148) administration were as follows. There was no significant difference in compliance (69% for IV v 71% for SC) in patients receiving a full dose of amifostine. Reasons for dose reduction were acute toxicity (25% for IV v 27% for SC; P = .51) and logistics (18% for IV v 9% for SC administration; P = .09). Acute toxicity differed significantly in terms of grade 1 to 2 hypotension (19% for IV v 8% for SC; P = .01), grade 1 to 2 skin rash (9% for IV v 21% for SC; P = .01), and local pain (0% for IV v 8% for SC; P = .003). The incidence of grade 2 or greater xerostomia was significantly higher for patients who received amifostine via SC administration (37% for IV v 62% for SC; P = .005) in the 127 patients (n = 67, IV; n = 60, SC) evaluable at 1 year but not at 2 or 3 years (36% for IV v 51% for SC administration; P = .19; 32% for IV v 41% for SC; P = .63). A generalized linear mixed-model analysis of all data revealed no significant difference in patient self-assessment of salivary function (P = .25), unstimulated or stimulated salivary flow rates (P = .054 and .82, respectively), or grade 2 or greater xerostomia (P = .23).


CONCLUSIONS
SC amifostine administration was not significantly superior to IV amifostine administration in terms of patient compliance or efficacy.
Department of Radiation Oncology, Centre Régional de Lutte Contre le Cancer Nantes-Atlantique René Gauducheau, Nantes, France. bardet@nantes.fnclcc.fr
Etienne
E
Bardet
Laurent
L
Martin
Gilles
G
Calais
Marc
M
Alfonsi
Nasr Eddine
NE
Feham
Claude
C
Tuchais
Pierre
P
Boisselier
Bernadette
B
Dessard-Diana
Sok-Hun
SH
Seng
Pascal
P
Garaud
Anne
A
Aupérin
Jean
J
Bourhis
D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage* / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D007262:Infusions, Intravenous; D055104:Infusions, Subcutaneous; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000009:adverse effects
D011837:Radiation-Protective Agents; D004999:Amifostine