Simplified Graded Infusion Strategy for Mitigation of Oxaliplatin Hypersensitivity

Published:January 18, 2022DOI:



      Hypersensitivity reactions (HSRs) to oxaliplatin present a therapeutic challenge. The standard desensitization protocol consists of 12 infusion steps with 3 drug dilutions, often in an inpatient setting. Several years ago we implemented a simplified outpatient graded infusion protocol for oxaliplatin with 2 drug dilutions and 3 infusion steps.

      Materials and Methods

      We performed a retrospective analysis of our experience to define the safety and outcomes associated with this simplified, ambulatory, graded infusion strategy.


      Between January 1, 2011 and December 1, 2020, 374 patients who had experienced an oxaliplatin-related HSR were treated via a 3-step graded infusion in the outpatient setting. Of these 374 patients, 283 (76%) did not experience a subsequent HSR, while 91 (24%) did experience a breakthrough HSR. Of the 374 patients, 19 (5%) experienced a grade 3 or 4 HSR. Three patients (0.8%) were hospitalized. There was no grade 5 (fatal) HSRs. Overall, the 374 patients received a median additional 3 cycles of oxaliplatin (range 1-41). The most common reasons for treatment discontinuation were disease progression (35%), breakthrough HSRs (24%), completion of treatment (21%), and toxicity other than HSR (20%). Fifteen patients who experienced breakthrough HSRs during a graded infusion were subsequently treated with the standard 12-step desensitization. Five of these 15 patients had an HSR during their initial desensitization and 5 developed an HSR on subsequent 12-step desensitizations. Thus, treatment was discontinued in 67% of these 15 patients due to persistent HSRs.


      Our data indicate that the simplified 3-step graded infusion protocol is a safe outpatient strategy for patients with a history of HSR to oxaliplatin.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Colorectal Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Graham J.
        • Mushin M.
        • Kirkpatrick P.
        Nat Rev Drug Discov. 2004; 3: 11-12
        • Andre T.
        • Boni C.
        • Mounedji-Boudiaf L.
        • Navarro M.
        • Tabernero J.
        Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer.
        N Engl J Med. 2004; 350: 2343-2351
        • Polyzos A.
        • Tsavaris N.
        • Gogas H.
        • Souglakos J.
        • Vambakas L.
        Clinical features of hypersensitivity reactions to oxaliplatin: a 10-year experience.
        Oncology. 2009; 76: 36-41
        • Suenaga M.
        • Mizunuma N.
        • Shinozaki E.
        • Matsusaka S.
        • Chin K.
        Management of allergic reactions to oxaliplatin in colorectal cancer patients.
        J Support Oncol. 2008; 6: 373-378
        • Siu S.W.
        • Chan R.T.
        • Au G.K
        Hypersensitivity reactions to oxaliplatin: experience in a single institute.
        Ann Oncol. 2006; 17: 259-261
        • Madrigal-Burgaleta R.
        • Berges-Gimeno M.P.
        • Angel-Pereira D.
        • Ferreiro-Monteagudo R.
        • Guillen-Ponce C.
        Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189 procedures with a new short protocol and novel diagnostic tools assessment.
        Allergy. 2013; 68: 853-861
        • Castells M.
        Rapid desensitization for hypersensitivity reactions to medications.
        Immunol Allergy Clin North Am. 2009; 29: 585-606
        • Castells M.C.
        • Tennant N.M.
        • Sloane D.E.
        • Hsu F.I.
        • Barrett N.A.
        Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases.
        J Allergy Clin Immunol. 2008; 122: 574-580
        • Lee C.W.
        • Matulonis U.A.
        • Castells M.C.
        Carboplatin hypersensitivity: a 6-h 12-step protocol effective in 35 desensitizations in patients with gynecological malignancies and mast cell/IgE-mediated reactions.
        Gynecol Oncol. 2004; 95: 370-376
        • Castells Guitart M.C
        Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century.
        J Investig Allergol Clin Immunol. 2014; 24: 72-79
        • Sloane D.
        • Govindarajulu U.
        • Harrow-Mortelliti J.
        • Barry W.
        • Hsu F.I.
        Safety, costs, and efficacy of rapid drug desensitizations to chemotherapy and monoclonal antibodies.
        J Allergy Clin Immunol Pract. 2016; 4: 497-504
        • O'Malley D.M.
        • Vetter M.H.
        • Cohn D.E.
        • Khan A.
        • Hays J.L.
        Outpatient desensitization in selected patients with platinum hypersensitivity reactions.
        Gynecol Oncol. 2017; 145: 603-610
        • Botsen D.
        • Lepoix E.
        • Mazza C.
        • Brasseur M.
        • Grange A.
        Oxaliplatin-desensitization procedure is safe and feasible in an outpatient cancer unit in France.
        Support Care Cancer. 2019; 27: 3179-3182
        • Cernadas J.R.
        • Brockow K.
        • Romano A.
        • Aberer W.
        • Torres M.J.
        General considerations on rapid desensitization for drug hypersensitivity - a consensus statement.
        Allergy. 2010; 65: 1357-1366
        • Desrame J.
        • Broustet H.
        • Darodes de Tailly P.
        • Girard D.
        • Saissy J.M
        Oxaliplatin-induced haemolytic anaemia.
        Lancet. 1999; 354: 1179-1180
        • Perez-Alzate D.
        • Blanca-Lopez N.
        • Somoza M.L.
        • Ruano F.J.
        • Montero G.S.
        Anaphylaxis and severe immune hemolytic anemia during the course of desensitization with carboplatin.
        Ann Allergy Asthma Immunol. 2018; 120: 442-443
        • Vyskocil J.
        • Tucek S.
        • Kiss I.
        • Fedorova L.
        • Nevrlka J.
        • Zdrazilova-Dubska L.
        Type II hypersensitivity reactions after oxaliplatin rechallenge can be life threatening.
        Int Immunopharmacol. 2019; 74105728