Clinical Features of Oxaliplatin Induced Hypersensitivity Reactions and Therapeutic Approaches

  • Bano, Nusrat (Pharmacology, King Saud bin Abdulaziz University of Health Sciences) ;
  • Najam, Rahila (Pharmacology, University of Karachi) ;
  • Qazi, Faaiza (Pharmaceutics, Jinnah Sindh Medical University) ;
  • Mateen, Ahmed (Clinical Oncology, Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN))
  • Published : 2016.06.01


Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan.


  1. Aroldi F, Prochilo T, Bertocchi P, et al (2015). Oxaliplatininduced hypersensitivity reaction: underlying mechanisms and management. J Chemother, 27, 63-6.
  2. Anderson BJ, Peterson LL (2015). Systemic capillary leak syndrome in a patient receiving adjuvant oxaliplatin for locally advanced colon cancer. J Oncol Pharm Pract, 12, 1078155215591388.
  3. Alvarez-Cuesta E, Madrigal-Burgaleta R, Angel-Pereira D, et al (2015). Delving into cornerstones of hypersensitivity to antineoplastic and biological agents: value of diagnostic tools prior to desensitization. Allergy, 70, 784-94.
  4. Arotcarena R, Berthelemy P, Piot M, et al (2001). Readministration of oxaliplatin using a rapid desensitization method after severe anaphylactic reaction. Gastroenterol Clin Biol, 25, 206-7.
  5. Alliot C, Messouak D, Beets C, et al (2001). Severe anaphylactic reaction to oxaliplatin. Clin Oncol (R Coll Radiol), 13, 236.
  6. Benedik J (2015). Hypersensitivity: case report. Reactions, 1534, 137.
  7. Bahl M, Dean T (2015). An intermediate step for the management of hypersensitivity to platinum and taxane chemotherapy. Curr Oncol, 22, 220.
  8. Brockow K, Przybilla B, Aberer W, et al (2015). Guideline for the diagnosis of drug hypersensitivity reactions. Allergo J Int, 24, 94-105.
  9. Bano N, Najam R, Qazi F, et al (2014). Gastrointestinal Adverse Effects in Advanced Colorectal Carcinoma Patients Treated with Different Schedules of FOLFOX. Asian Pac J Cancer Prev, 15, 8089-93.
  10. Boulanger J, Boursiquot JN, Cournoyer G, et al (2014). Comite de l’evolution des pratiques en oncologie. Curr Oncol, 21, 630-41.
  11. Baretta Z, Falci C, Piva E et al (2013). Fatal oxaliplatin-induced thrombotic thrombocytopenic purpura: a case report. Clin Colorectal Cancer, 4, 294-96.
  12. Breslow RG, Caiado J, Castells MC (2009). Acetylsalicylic acid and montelukast block mast cell mediator-related symptoms during rapid desensitization. Ann Allergy Asthma Immunol, 102, 155-60.
  13. Caiado J, Castells M (2015). Presentation and diagnosis of hypersensitivity to platinum drugs. Curr Allergy Asthma Rep, 15, 1-9.
  14. Cheng LC, Chen HH, Lin SE, et al (2008). Hypersensitivity reactions to oxaliplatin: a prospectively collected study of 25 cases treated in one institute. J Soc Colon Rectal Surgeon (Taiwan), 19, 115-21.
  15. Cobo F, De Celis G, Pereira A, et al (2007). Oxaliplatin-induced immune hemolytic anemia: a case report and review of the literature. Anti-Cancer Drugs, 18, 973-6.
  16. Curtis BR, Kaliszewski J, Marques MB, et al (2006). Immunemediated thrombocytopenia resulting from sensitivity to oxaliplatin. Am J Hematol, 81, 193-8.
  17. Dodgshun AJ, Hansford JR, Cole T, et al (2016). Carboplatin hypersensitivity reactions in pediatric low grade glioma are protocol specific and desensitization shows poor efficacy. Pediatr Blood Cancer, 63, 17-20.
  18. De Vries RS, Mattijssen EJ, van Sorge AA, (2006). Serious delayed hypersensitivity reaction to oxaliplatin. Ann oncol, 17, 1723-4.
  19. De Gramont A, Vignoud J, Tournigand C, et al (1997). Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hours continuous infusion in pre-treated metastatic colorectal cancer. Eur J Cancer, 33, 214-9.
  20. Florit-Sureda M, Conde-Estevez D, Vidal J, et al (2015). Hypersensitivity reaction caused by folinic acid administration: a case report and literature review. J Chemother. [Epub ahead of print]
  21. Forcello NP, Khubchandani S, Patel SJ, et al (2015). Oxaliplatininduced immune-mediated cytopenias: A case report and literature review. J Oncol Pharm Pract, 21, 148-56.
  22. Giavina-Bianchi P, Aun MV, Galvao VR, et al (2015). Rapid Desensitization in Immediate Hypersensitivity Reaction to Drugs. Curr Treat Options Allergy, 2, 268-85.
  23. Gutierrez M, Pautier P, Lhomme C, et al (2002). Replacement of carboplatin by oxaliplatin may be one solution for patients treated for ovarian carcinoma who are hypersensitive to carboplatin. J Clin Oncol, 20, 353.
  24. Gerard B, Bleiberg H, Van Daele D, et al (1998). Oxaliplatin combined to 5-fluorouracil and folinic acid: an effective therapy in patients with advanced colorectal cancer. Anticancer Drugs, 9, 301-05.
  25. Ichikawa Y, Goto A, Hirokawa S, et al (2009). Allergic reactions to oxaliplatin in a single institute in Japan. Jpn J Clin Oncol, 39, 616-20.
  26. Kim JY, Lim KH, Song WJ, et al (2015). Breakthrough Reactions during Oxaliplatin Desensitization: An Analysis of 177 Cases. J Allergy Clin Immunol, 135, 112.
  27. Kumaran D, Rupa D, Haresh KP, et al (2015). Oxaliplatin induced pulmonary toxicity-a rare phenomenon. Cancer Treat Commun, 4, 203-5.
  28. Kurian S, Macintyre J, Mushtaq M, et al (2012). Oxaliplatin induced disseminated intravascular coagulation: A case report and review of literature. World J Gastrointest Oncol, 4, 181.
  29. Lee SY, Kim MY, Kim MH, et al (2013). Hypersensitivity reactions to oxaliplatin: outcomes of premedication and desensitization. J Allergy Clin Immunol, 131, 166.
  30. Lundqvist EÅ, Fujiwara K, Seoud M (2015). Principles of chemotherapy. Int J Gynaecol Obstet, 131, 146-9.
  31. Leguy-Seguin V, Jolimoy G, Coudert B, et al (2007). Diagnostic and predictive value of skin testing in platinum salt hypersensitivity, J Allergy Clin Immunol, 119, 726-30.
  32. Lenz HJ (2007). Management and preparedness for infusion and hypersensitivity reactions. Oncologist, 12, 601-9.
  33. Larzilliere I, Brandissou S, Breton P, et al (1999). Anaphylactic reaction to oxaliplatin: a case report. Am J Gastroenterol, 94, 3387-8.
  34. Malkhasyan K, Halene S, Lacy J, et al (2015). Oxaliplatin- Related Acute Disseminated Intravascular Coagulation Syndrome in a Patient With Metastatic Colon Cancer. Clin Colorectal Cancer, 14, 9-12.
  35. Madrigal-Burgaleta R, Berges-Gimeno MP, Angel-Pereira D, et al (2013). Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189 procedures with a new short protocol and novel diagnostic tools assessment. Allergy, 68, 853-61.
  36. Meyer L, Zuberbier T, Worm M, et al (2002). Hypersensitivity reactions to oxaliplatin: cross-reactivity to carboplatin and the introduction of a desensitization schedule [letter]. J Clin Oncol, 20, 1146-7.
  37. Markman M, Kennedy A, Webster K, et al (1999). Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol, 17, 1141-5.
  38. Maindrault-Goebel F, Louvet C, Andre T, et al (1999). Oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX6). GERCOR. Eur J Cancer, 35, 1338-42.
  39. Machover D, Diaz-Rubio E, de Gramont A, et al (1999). Two consecutive phase II studies of oxaliplatin (L-OHP) for treatment of patients with advanced colorectal carcinoma who were resistant to previous treatment with fluoropyrimidines. Ann Oncol, 7, 95-8.
  40. Nisi C, Moretti A, Donati D, et al (2015). E18A post-reaction regimen for CRC patients manifesting hypersensitivity to oxaliplatin: an effective alternative not to rule out an important option of treatment. Ann Oncol, 26, 41.
  41. Okayama T, Ishikawa T, Sugatani K, et al (2015). Hypersensitivity reactions to oxaliplatin: identifying the risk factors and judging the efficacy of a desensitization protocol. Clin Ther, 37, 1259-69.
  42. Osumi H, Shinozaki E, Kumekawa Y, et al (2013). Three cases of fatal thrombocytopenia after oxaliplatin-based chemotherapy. Gan Kagaku Ryoho, 40, 1557-60.
  43. Pedersen KS (2015). Safety and efficacy of desensitization protocols for platinum hypersensitivity reactions. Pancreas, 2, 10.
  44. Pagani M (2015). Hypersensitivity, urticaria and dyspnoea: 6 case reports. Reactions, 1567, 168-5.
  45. Parel M, Ranchon F, Nosbaum A, (2014). Hypersensitivity to oxaliplatin: clinical features and risk factors. BMC Pharmacol Toxicol, 15, 1.
  46. Polyzos A, Tsavaris N, Kosmas C, et al (2001). Hypersensitivity reactions to carboplatin administration are common but not always severe: a 10-year experience. Oncol, 61, 129-33.
  47. Syrigou EI (2015). Hypersensitivity reaction: case report. Reactions, 1533, 343-10.
  48. Santini D, Tonini G, Salerno A, et al (2001). Idiosyncratic reaction after oxaliplatin infusion [letter]. Ann Oncol, 12, 132-3.
  49. Schüll B, Kornek GV, Scheithauer W (2001). Idiosyncratic reaction after oxaliplatin: circumvention by use of a continuous infusional administration schedule. Ann Oncol. 12, 1653-4.
  50. Shukunami K, Kurokawa T, Kubo M, et al (1999). Hypersensitivity reaction to carboplatin during treatment for ovarian cancer: successful resolution by replacement with cisplatin. Tumori, 85, 297-8.
  51. Shlebak AA, Clark PI, Green JA (1995).Hypersensitivity and cross reactivity to cisplatin and analogues. Cancer Chemother Pharmacol, 35, 349-51.
  52. Spearing RL, Hickton CM, Sizeland P, et al (1990). Quinineinduced disseminated intravascular coagulation. Lancet, 336, 1535-7.
  53. Tham EH, Cheng YK, Tay MH, et al (2015). Evaluation and management of hypersensitivity reactions to chemotherapy agents. Postgrad Med J, 91, 145-50.
  54. Tamura H (2015). Anaphylactic shock leading to cardiopulmonary arrest: case report. Reactions, 1552, 171-23.
  55. Toki MI, Saif MW, Syrigos KN (2014). Hypersensitivity reactions associated with oxaliplatin and their clinical management. Expert Opin Drug Saf, 13, 1545-54.
  56. Taleghani BM, Meyer O, Fontana S, et al (2005). Oxaliplatininduced immune pancytopenia. Transfusion, 45, 704-8.
  57. Thomas RR, Quinn MG, Schuler B, et al (2003). Hypersensitivity and idiosyncratic reactions to oxaliplatin. Cancer, 97, 2301-7.
  58. Tonini G, Santini D, Vincenzi B, et al (2002). Oxaliplatin may induce cytokine-release syndrome in colorectal cancer patients. J Biol Regul Homeost Agents, 16, 105-9.
  59. Tournigand C, Maindrault-Goebel F, Louvet C, et al (1998). Severe anaphylactic reactions to oxaliplatin. Eur J Cancer, 34, 1297-8.
  60. Wang AL, Patil SU, Long AA, et al (2015). Risk-stratification protocol for carboplatin and oxaliplatin hypersensitivity: repeat skin testing to identify drug allergy. Ann Allergy Asthma Immunol, 115, 422-8.
  61. Wang JH, King TM, Chang MC, et al (2012). Oxaliplatin-induced severe anaphylactic reactions in metastatic colorectal cancer: case series analysis. World J Gastroenterol, 18, 5427-33.
  62. Yamauchi H, Goto T, Takayoshi K, et al (2015). A retrospective analysis of the risk factors for allergic reactions induced by the administration of oxaliplatin. Eur J Cancer Care, 24, 111-6.
  63. Yanagihara Y (2015). Allergic reaction and fever: 2 case reports. Reactions, 1555, 147-3.
  64. Yoshida Y, Hirata K, Matsuoka H, et al (2015). A single-arm Phase II validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: the aVOiD trial. Drug Des Devel Ther, 9, 6067-73.
  65. Zanotti KM, Rybicki LA, Kennedy AW, et al (2001). Carboplatin skin testing: a skin-testing protocol for predicting hypersensitivity to carboplatin chemotherapy. J Clin Oncol, 19, 3126-9.

Cited by

  1. Comparison between hypersensitivity reactions to cycles of modified FOLFOX6 and XELOX therapies in patients with colorectal cancer vol.79, pp.5, 2017,
  2. Chemotherapy Acute Infusion Reactions: A Qualitative Report of the Perspectives of Patients With Cancer vol.35, pp.11, 2018,