High-dose dexamethasone plus antihistamine prevents colorectal cancer patients treated with modified FOLFOX6 from hypersensitivity reactions induced by oxaliplatin

Int J Clin Oncol. 2011 Jun;16(3):244-9. doi: 10.1007/s10147-010-0170-6. Epub 2011 Jan 18.

Abstract

Background: Oxaliplatin is a third-generation platinum compound and a key agent for the management of colorectal cancer. Patients treated with oxaliplatin are at risk for hypersensitivity reactions. We designed a modified premedication regimen to prevent oxaliplatin-related hypersensitivity reactions and assessed if this approach is effective.

Methods: A retrospective cohort study of patients with advanced colorectal cancer who received modified FOLFOX6 (mFOLFOX6) was performed. Patients received routine premedication with dexamethasone 8 mg and granisetron 3 mg for the first five cycles of mFOLFOX6. From the sixth cycle onward, cohort 1 received the same premedication, and cohort 2 received modified premedication (diphenhydramine 50 mg orally, followed by dexamethasone 20 mg, granisetron 3 mg, and famotidine 20 mg). We compared the incidence of hypersensitivity reactions, duration of treatment, and reasons for treatment withdrawal between the two cohorts.

Results: A total of 181 patients were studied (cohort 1, 81; cohort 2, 100). Hypersensitivity reactions developed in 16 patients (20%) in cohort 1 and 7 (7.0%) in cohort 2 (P = 0.0153). The median number of cycles increased from 9 in cohort 1 to 12 in cohort 2. Apart from progressive disease, neurotoxicity was the reason for discontinuing treatment in 20% of the patients in cohort 1, as compared with 53% in cohort 2.

Conclusion: Increased doses of dexamethasone and antihistamine significantly reduced oxaliplatin-related hypersensitivity reactions. This effective approach should be considered for all patients who receive FOLFOX, allowing treatment to be completed as planned.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Anti-Allergic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cohort Studies
  • Colorectal Neoplasms / drug therapy*
  • Desensitization, Immunologic
  • Dexamethasone / administration & dosage
  • Drug Hypersensitivity / drug therapy*
  • Drug Hypersensitivity / etiology
  • Drug Hypersensitivity / prevention & control
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Histamine Antagonists / administration & dosage*
  • Humans
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects*
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Premedication
  • Retrospective Studies

Substances

  • Anti-Allergic Agents
  • Histamine Antagonists
  • Organoplatinum Compounds
  • Oxaliplatin
  • Dexamethasone
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol