title: Successful re-challenge with panitumumab in patients who developed hypersensitivity reactions to cetuximab: report of three cases and review of literature.
abstract: BACKGROUND
  Monoclonal antibodies (MAbs) targeting epidermal growth factor receptor (EGFR) are effective in treatment of metastatic colorectal cancer (mCRC). Cetuximab, a chimeric MAb targets EGFR. Even with premedication, cetuximab can cause a hypersensitivity reaction (HSR). In case of severe HSR, further therapy with cetuximab is contraindicated, thus preventing these patients from receiving potentially beneficial anti-EGFR therapy. Panitumumab is a fully human MAb also targets EGFR. To date, no human antihuman Ab have been detected, and unlike CET, HSR are infrequent, and no premedication is required. Safety of panitumumab in patients with a previous severe HSR with cetuximab is not fully known. We present three patients with GI cancers who tolerated panitumumab without HSR after experiencing severe HSR to cetuximab.
  
  
  METHODS
  Three patients were challenged with standard dose of panitumumab (6 mg/kg) after experiencing grade 3 HSR to standard dose of cetuximab under strict observation and no premedication. First patient, a 58-year-old male with mCRC developed grade 3 HSR during 8th dose of cetuximab. Second patient was a 58-year-old female with mCRC developed grade 3 HSR during 12th dose of cetuximab. Third patient was a 61-year-old male with pancreatic cancer who experienced grade 3 HSR during loading dose of cetuximab. Charts were reviewed to find history of prior allergy, including H1 blocker use, drug allergy, bee sting allergy, eczema, allergic reactive airways disease, or food allergy.
  
  
  RESULTS
  All patients were Caucasians with an average age of 59 year with no history of prior allergy. No patient received any premedication. First patient received panitumumab for 2 months, second patient was treated for 6 months, and third patient who was rechallenged 1 week after HSR to cetuximab had a partial response following 6 months of therapy.
  
  
  CONCLUSIONS
  HSR are serious complications associated with MAbs. Thanks to hybridoma technology that newer generations of MAbs contain less or no mouse-specific protein sequences, hence reducing the risk of HSR. Identification of individuals likely to develop severe and sometimes life-threatening HSR is challenging. Our report of three patients successfully treated with panitumumab after they had severe HSR to cetuximab warrant further investigation.
authors.affiliation: Section of Medical Oncology, Yale University School of Medicine, 333 Cedar Street, FMP 116, New Haven, CT 06520, USA. wasif.saif@yale.edu
authors.forename: Muhammad Wasif
authors.initials: MW
authors.lastname: Saif
authors.forename: J
authors.initials: J
authors.lastname: Peccerillo
authors.forename: Von
authors.initials: V
authors.lastname: Potter
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004342:Drug Hypersensitivity / Q000209:etiology / Q000517:prevention & control*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D000077544:Panitumumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab