Toxicity of oxaliplatin rechallenge in metastatic colorectal cancer
Authors: G. Mauri, K. Bencardino, A. Sartore-Bianchi, S. Siena
Journal: Annals of Oncology (2018)

We have read with great interest the article published by Arnold et al. [1.Arnold D. Prager G.W. Quintela A. et al.Beyond second-line therapy in patients with metastatic colorectal cancer: a systematic review.Ann Oncol. 2018; 29: 835-856Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar] in which the authors systematically reviewed the options of treatment in patients with metastatic colorectal cancer (mCRC) beyond second line of therapy. Reviewed data supported the use of approved agents such as regorafenib or trifluridine/tipiracil rather than any chemotherapy rechallenge based on evidences of efficacy and safety derived from clinical trials [1.Arnold D. Prager G.W. Quintela A. et al.Beyond second-line therapy in patients with metastatic colorectal cancer: a systematic review.Ann Oncol. 2018; 29: 835-856Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar]. In their study, according to the criteria of systematic review of the paper, authors mentioned rechallenge with oxaliplatin by reporting survival data and ≥G3 toxicities from available phase II/III clinical trials but they have omitted to consider the occurrence of oxaliplatin immune-induced syndrome (OIIS). As described by our group and others, OIIS is a rare but potentially life-threatening side-effect characterized by acute onset of thrombocytopenia, fever, renal failure, hemolytic anemia, chills, back pain, and bleeding arising within 24 h from oxaliplatin administration [2.Bencardino K. Mauri G. Amatu A. et al.Oxaliplatin immune-induced syndrome occurs with cumulative administration and rechallenge: single institution series and systematic review study.Clin Colorectal Cancer. 2016; 15: 213-221Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar, 3.Cobo F. De Celis G. Pereira A. et al.Oxaliplatin-induced immune hemolytic anemia: a case report and review of the literature.Anticancer Drugs. 2007; 18: 973-976Crossref PubMed Scopus (34) Google Scholar, 4.Phull P. Quillen K. Hartshorn KL. Acute oxaliplatin-induced hemolytic anemia, thrombocytopenia, and renal failure: case report and a literature review.Clin Colorectal Cancer. 2017; 16: e105Abstract Full Text Full Text PDF Scopus (5) Google Scholar]. In four cases described in the literature, OIIS was lethal [2.Bencardino K. Mauri G. Amatu A. et al.Oxaliplatin immune-induced syndrome occurs with cumulative administration and rechallenge: single institution series and systematic review study.Clin Colorectal Cancer. 2016; 15: 213-221Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar]. OIIS has been associated with long-term administration of oxaliplatin, occurring most frequently after an average of 16th cycles of oxaliplatin-based regimens [2.Bencardino K. Mauri G. Amatu A. et al.Oxaliplatin immune-induced syndrome occurs with cumulative administration and rechallenge: single institution series and systematic review study.Clin Colorectal Cancer. 2016; 15: 213-221Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar]. Interestingly, OIIS has been demonstrated to occur earlier if discontinuation and subsequent reintroduction of oxaliplatin takes place. OIIS occurs indeed after average four cycles of rechallenge with oxaliplatin, therefore earlier than with continuous administration within the same therapeutic line [2.Bencardino K. Mauri G. Amatu A. et al.Oxaliplatin immune-induced syndrome occurs with cumulative administration and rechallenge: single institution series and systematic review study.Clin Colorectal Cancer. 2016; 15: 213-221Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar]. The mechanisms underlying OIIS have not been clarified yet, but drug specific antibody production is currently under investigation as the most plausible. Recently, OIIS has been associated with multiple drug-dependent antibodies sensitizing to several compounds and thus potentially jeopardizing continuation of other oncological treatments beyond oxaliplatin [5.Curtis B.R. Hsu Y.-M.S. Podoltsev N. et al.Patients treated with oxaliplatin are at risk for thrombocytopenia caused by multiple drug-dependent antibodies.Blood. 2018; 131: 1486-1489Crossref PubMed Scopus (11) Google Scholar]. All in all, these evidence the need to consider the risk of OIIS, rare and therefore insidious side-effect that may complicate treatment of patients with mCRC beyond second line. Authors are supported by grants from Associazione Italiana Ricerca Cancro grant AIRC 5 x mille [Project ID 51000] Special Program Molecular Clinical Oncology, AIRC Investigator Grant [Project ID 20685], and AIRC 5 x mille [Project ID 21091] Special Program Metastases; CORDIS Community Research and Development Information Service, Horizon 2020 [Project ID 635342] grant Molecularly Guided Trials with Specific Treatment Strategies in Patients with Advanced Newly Molecular Defined Subtypes of Colorectal Cancer (MoTriColor); Fondazione Oncologia Niguarda Onlus, grant Terapia Molecolare dei Tumori, and grant Studies to Develop Therapies Against Colorectal Cancer in Young Adults.