title: Successful desensitization protocol for hypersensitivity reaction probably caused by dabrafenib in a patient with metastatic melanoma.
abstract: Vemurafenib and dabrafenib are both orally bioavailable small molecule agents that block mitogen activated protein kinase signalling in patients with melanoma and BRAF(V600E) mutation. Generalized hypersensitivity reactions to vemurafenib or dabrafenib have not been described. Continuing vemurafenib or dabrafenib therapy despite hypersensitivity reaction is especially important in patients with melanoma and BRAF(V600E) mutation, in whom this mutation plays a critical role in tumour growth. Desensitization protocols to overcome hypersensitivity reactions by gradual reintroduction of small amounts of the offending drug up to full therapeutic doses are available for many anti-cancer agents, including vemurafenib but, to the best of our knowledge, have not been reported for dabrafenib. We describe a patient with metastatic melanoma who developed Type I hypersensitivity reaction to vemurafenib and to subsequent treatment with dabrafenib, and who was successfully treated by drug desensitization which allowed safe prolonged continuation of dabrafenib. The development of hypersensitivity reactions for both dabrafenib and vemurafinib in the current case could be because these drugs have a similar chemical structure and cause a cross-reactivity. However, hypersensitivity reaction to a non-medicinal ingredient shared by the two drugs is also possible. Oral desensitization appears to be an option for patients with hypersensitivity Type I to dabrafenib. This approach may permit clinicians to safely administer dabrafenib to patients who experience hypersensitivity reactions to this life-prolonging medication.
authors.affiliation: Division of Oncology, Technion-Israel Institute of Technology, Haifa g_barsela@rambam.health.gov.il.
authors.forename: Gil
authors.initials: G
authors.lastname: Bar-Sela
authors.affiliation: Division of Oncology, Technion-Israel Institute of Technology, Haifa.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abu-Amna
authors.affiliation: Pharmacy Department, Technion-Israel Institute of Technology, Haifa.
authors.forename: Salim
authors.initials: S
authors.lastname: Hadad
authors.affiliation: Division of Oncology, Technion-Israel Institute of Technology, Haifa.
authors.forename: Nissim
authors.initials: N
authors.lastname: Haim
authors.affiliation: Department of Immunology, Rambam Health Care Campus and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Shahar
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy / Q000556:secondary; D003888:Desensitization, Immunologic; D003907:Dexamethasone / Q000627:therapeutic use; D004155:Diphenhydramine / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000188:drug therapy / Q000209:etiology; D005260:Female; D005720:Gamma Rays; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D010091:Oximes / Q000009:adverse effects / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014057:Tomography, X-Ray Computed
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D007093:Imidazoles; D010091:Oximes; D003907:Dexamethasone; D004155:Diphenhydramine; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib
keywords: dabrafenib; desensitization; hypersensitivity reaction; vemurafenib