title: Hypersensitivity Reactions to Oxaliplatin: Identifying the Risk Factors and Judging the Efficacy of a Desensitization Protocol.
abstract: OBJECTIVE
  We examined the clinical data of patients treated with oxaliplatin to determine the risk factors of oxaliplatin-related hypersensitivity reaction (HSR). In addition, we evaluated the efficacy of rechallenging patients with HSRs with oxaliplatin using prophylactic agents or desensitization procedures.
  
  
  METHODS
  This study consisted of 162 patients with colorectal cancer (88 men and 74 women) who were treated consecutively at the outpatient chemotherapy department at University Hospital, Kyoto Prefectural University of Medicine. Patients underwent chemotherapy, including oxaliplatin, between March 2006 and June 2012. We analyzed the patients' clinical backgrounds (eg, age, sex, performance status, disease stage, and allergic history) to uncover any connections to the development of HSR to oxaliplatin. In addition, we rechallenged 10 patients who had oxaliplatin-related HSR using prophylactic agents or desensitization procedures.
  
  
  RESULTS
  Of 162 patients, 28 (17.2%) developed oxaliplatin-related HSRs (16, 2, 9 and 1 patient had grade 1, 2, 3, and 4 HSRs, respectively). The total cumulative dose of oxaliplatin at the onset of the HSR was 301 to 1126 mg/m(2) (median, 582 mg/m(2)), and the first reactions developed in these patients after 5 to 17 infusions of oxaliplatin (median, 8 infusions). Logistic regression analysis indicated that sex (male: odds ratio = 3.624; 95% CI, 1.181-11.122; P = 0.024) and eosinophil count in peripheral blood (odds ratio = 35.118; 95% CI, 1.058-1166.007; P = 0.046) were independent variables for oxaliplatin-related HSRs. Rechallenging patients with prophylactic agents was successful in 2 (28.6%) of 7 patients who successfully completed their treatment. On the other hand, all 3 patients rechallenged with oxaliplatin using a desensitization protocol successfully completed their treatment without new HSRs.
  
  
  CONCLUSIONS
  In this retrospective study, we observed that being male and having higher counts of peripheral eosinophil could be predictors for HSR to oxaliplatin. In addition, this study confirms that oxaliplatin desensitization protocol allows patients who developed HSRs to continue with their treatment. However, the optimum desensitization protocol for oxaliplatin administration in terms of tolerability and efficacy needs to be defined.
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Cancer ImmunoCell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Tetsuya
authors: T
authors: Okayama
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Cancer ImmunoCell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: iskw-t@koto.kpu-m.ac.jp.
authors: Takeshi
authors: T
authors: Ishikawa
authors: Medical Oncology, Kyoto Prefectural University Hospital, Kyoto, Japan.
authors: Kazuko
authors: K
authors: Sugatani
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Medical Oncology, Kyoto Prefectural University Hospital, Kyoto, Japan.
authors: Naohisa
authors: N
authors: Yoshida
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Cancer ImmunoCell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Satoshi
authors: S
authors: Kokura
authors: Medical Oncology, Kyoto Prefectural University Hospital, Kyoto, Japan.
authors: Kiyomi
authors: K
authors: Matsuda
authors: Medical Oncology, Kyoto Prefectural University Hospital, Kyoto, Japan.
authors: Shigeru
authors: S
authors: Tsukamoto
authors: Medical Oncology, Kyoto Prefectural University Hospital, Kyoto, Japan.
authors: Norihiko
authors: N
authors: Ihara
authors: Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Yoshiaki
authors: Y
authors: Kuriu
authors: Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Masayoshi
authors: M
authors: Nakanishi
authors: Medical Oncology, Kyoto Prefectural University Hospital, Kyoto, Japan; Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Terukazu
authors: T
authors: Nakamura
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Kazuhiro
authors: K
authors: Kamada
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Kazuhiro
authors: K
authors: Katada
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Kazuhiko
authors: K
authors: Uchiyama
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Tomohisa
authors: T
authors: Takagi
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Osamu
authors: O
authors: Handa
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Hideyuki
authors: H
authors: Konishi
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Nobuaki
authors: N
authors: Yagi
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Yuji
authors: Y
authors: Naito
authors: Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Eigo
authors: E
authors: Otsuji
authors: Medical Oncology, Kyoto Prefectural University Hospital, Kyoto, Japan; Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Hajime
authors: H
authors: Hosoi
authors: Medical Oncology, Kyoto Prefectural University Hospital, Kyoto, Japan; Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Tsuneharu
authors: T
authors: Miki
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Yoshito
authors: Y
authors: Itoh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002452:Cell Count; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy*; D003888:Desensitization, Immunologic / Q000379:methods; D004342:Drug Hypersensitivity / Q000209:etiology*; D004804:Eosinophils; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin
keywords: colorectal cancer; desensitization; hypersensitivity reaction; oxaliplatin