title: Amifostine before chemotherapy: improved tolerance profile of the subcutaneous over the intravenous route.
abstract: BACKGROUND
  The i.v. administration of the cytoprotective agent amifostine is associated with reversible clinical hypotension, protracted emesis, and malaise in a various percentage of patients. We evaluated, prospectively, whether the s.c. route is a better tolerated alternative to the i.v. route in patients receiving chemotherapy.
  
  
  METHODS
  Fifty-nine patients treated with "once every 2 weeks" regimens received 1000 mg of amifostine i.v. before chemotherapy. Patients who developed protracted vomiting and malaise and/or clinical hypotension for two consecutive i.v. administrations received the same dose of amifostine s.c. for the subsequent cycles (i.v./s.c. study). In an additional cohort of 12 patients (s.c. study), 1000 mg of amifostine were given s.c. since the first chemotherapy cycle.
  
  
  RESULTS
  In the i.v./s.c. study, 8 (13.5%) patients showed protracted emesis/malaise and/or clinical hypotension during the first two cycles. An additional 4 (6.6%) patients developed similar side effects during the subsequent cycles. Switching to the s.c. route, an improved tolerance was noted. In the s.c. study, a total of 76 injections was administered. Protracted vomiting or clinical hypotension was absent, and this tolerance profile was significantly better than the i.v. one (P = 0.001). There were no other systemic side effects related to the s.c. administration.
  
  
  CONCLUSIONS
  Amifostine, at a dose of 1000 mg, is better tolerated when administered s.c. Switching to the s.c. route in patients with poor tolerance using the i.v. administration allows the continuation of cytoprotection with minor side effects. Although preliminary, 1000 mg of amifostine effectively protected against the lower, still more frequently administered doses of chemotherapy given once every 2 weeks.
authors.affiliation: Democritus University of Thrace Department of Radiotherapy-Oncology, Pneumology, Gynecology and Surgery, Alexandroupolis 68100, Greece.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: Costantinos
authors.initials: C
authors.lastname: Simopoulos
authors.forename: George
authors.initials: G
authors.lastname: Minopoulos
authors.forename: George
authors.initials: G
authors.lastname: Patlakas
authors.forename: Alexandros
authors.initials: A
authors.lastname: Polychronidis
authors.forename: Vassilis
authors.initials: V
authors.lastname: Limberis
authors.forename: Kostantinos
authors.initials: K
authors.lastname: Romanides
authors.forename: Michael
authors.initials: M
authors.lastname: Pitiacoudis
authors.forename: Costantinos
authors.initials: C
authors.lastname: Manolas
mesh_terms: D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014839:Vomiting / Q000188:drug therapy
chemical_list: D011837:Radiation-Protective Agents; D004999:Amifostine