title: A single-arm Phase II validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: the AVOID trial.
abstract: BACKGROUND
  Patients with colorectal cancer treated with oxaliplatin are at risk of hypersensitivity reactions, with the incidence estimated to be 12%-20%. Coinfusion of dexamethasone and oxaliplatin could potentially reduce the incidence of these reactions, but oxaliplatin is reported to be incompatible with alkaline compounds in solution. However, in a previous retrospective study we found that the pH of a solution of dexamethasone and oxaliplatin was less than 7.4, and that hypersensitivity to oxaliplatin could have been prevented by coinfusion of dexamethasone. We aimed to evaluate the effectiveness of coinfusion of dexamethasone and oxaliplatin to prevent oxaliplatin-induced hypersensitivity reactions.
  
  
  METHODS
  The AVOID trial was a prospective, multicenter, open-label, single-arm Phase II trial conducted from January to September 2013. The study included 73 patients who received capecitabine plus oxaliplatin (XELOX) or XELOX plus bevacizumab therapy for colorectal cancer. In all patients, oxaliplatin was administered in combination with dexamethasone. The primary outcome measure was the presence of hypersensitivity reactions.
  
  
  RESULTS
  Hypersensitivity reactions occurred in three patients (4.1%); all three experienced a cutaneous reaction (grade 1 erythema). None of the 73 patients developed respiratory symptoms, ocular symptoms, or anaphylaxis. Grade 3 or higher hemotoxicity occurred in 13.7% of the patients and grade 3 or higher nonhematological toxicity occurred in 13.7%. The response rate to treatment was 64.4%.
  
  
  CONCLUSIONS
  The coinfusion of dexamethasone and oxaliplatin effectively reduced oxaliplatin-induced hypersensitivity reactions in patients with colorectal cancer. This approach should be considered for all patients treated with oxaliplatin, allowing treatment to be completed as planned.
authors.affiliation: Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Surgery, Fukuoka Sanno Hospital, Fukuoka, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuoka
authors.affiliation: Department of Surgery, Kansai Medical University Hirakata Hospital, Osaka, Japan.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Iwamoto
authors.affiliation: Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Kotaka
authors.affiliation: Department of Surgical Oncology, Kanazawa Medical University, Uchinada, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Fujita
authors.affiliation: Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Aisu
authors.affiliation: Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Hoshino
authors.affiliation: Department of Surgical Oncology, Kanazawa Medical University, Uchinada, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Kosaka
authors.affiliation: Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Academia, Industry and Government Collaborative Research Institute of Translational Medicine for Life Innovation, Fukuoka University, Fukuoka, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Kiyomi
authors.affiliation: Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yamashita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000627:therapeutic use; D000069287:Capecitabine / Q000008:administration & dosage / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004338:Drug Combinations; D004342:Drug Hypersensitivity / Q000150:complications / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000069287:Capecitabine; D003907:Dexamethasone
keywords: allergy; dexamethasone; hypersensitivity; oxaliplatin