Oxaliplatin-Induced Fever and Release of IL-6

Abstract

Background: Oxaliplatin is a novel cytotoxic agent with documented activity in colorectal cancer. Side effects are generally moderate, and include peripheral neuropathy along with mild bone marrow suppression and gastrointestinal side effects. To our knowledge, induction of febrile episodes by this agents has not been described in the literature. Case Report: We present the case of a 74-year-old male patient admitted to our institution for palliative treatment of metastatic colorectal carcinoma. Due to progression during treatment with 5-fluorouracil and leucovorin, chemotherapy consisting of oxaliplatin 85 mg/m² on days 1 + 15 plus mitomycin C 8 mg/m² on day 1 repeated every 28 days was initiated. The first cycle of this combination was tolerated without side effects, but the patient experienced fever up to 39°C starting 2 h after oxaliplatin administration on day 15 of the second cycle, which persisted for 3 days. Fever again recurred at the same interval following administration of oxaliplatin on day 1 of the next cycle. Blood samples taken at regular intervals disclosed an increase in IL-6 serum levels parallel to the body temperature curve, with the peak corresponding to the highest temperature, while C-reactive protein values remained unchanged. In spite of intensive premedication with steroids, antipyretics and clarithromycin, fever promptly recurred during the third cycle of treatment. Conclusion: Our data suggest a clear- cut correlation between fever, the release of IL-6 and oxaliplatin administration. Whether IL-6 release is directly triggered by the application of oxaliplatin or is a bystander phenomenon, however, remains unclear at the moment.

Oxaliplatin-Induced Acute-Onset Thrombocytopenia, Hemorrhage and Hemolysis

“…However, it is unclear whether the reaction could be associated with the hematological serious adverse event. Other studies have shown that idiosyncratic reactions observed in colorectal cancer patients after oxaliplatin administration may be due to a massive release of cytokines such as TNF-α and IL-6 [9, 10]. In our case, we found an association between the reaction and increased levels of TNF-α and IL-10.…”

Life-threatening oxaliplatin-induced acute thrombocytopenia, hemolysis and bleeding: A case report

“…By contrast, other authors reported high levels of cytokines (i.e. IL6, IL10 and TNFa) suggesting that this l-OHP-dependent toxicity may be triggered by a massive release of pro-inflammatory molecules [8,15]. Interestingly, in this perspective Tonini et al, described a cytokine-release syndrome with chills, high fever, hypotension, abdominal pain, nausea, often diarrhea, but no signs of thrombocytopenia or hemolysis in patients treated with long-term l-OHPcontaining chemotherapy [16].…”

Fever as the only manifestation of hypersensitivity reactions associated with oxaliplatin in a patient with colorectal cancer Oxaliplatin-induced hypersensitivity reaction

“…In another study among 39 patients who received a FOLFOX regimen in first line or beyond, the most common manifestations of an allergic reaction included: respiratory (50%), cutaneous (40%), and an anaphylactic shock (7.6%) [20] . Ulrich-Pur et al [21] reported a case of 74-year-old man who developed fever hours after receiving the third infusion of oxaliplatin th to 6 th infusion. A rise in serum levels of IL 6 levels with 5 th and 6 th infusion corresponded to the rise in temperature.…”