Cancer Immunology, Immunotherapy

, Volume 64, Issue 3, pp 349–355 | Cite as

Fever and the use of paracetamol during IL-2-based immunotherapy in metastatic melanoma

  • Anne Helene KøstnerEmail author
  • Mai-Britt Bjørklund Ellegaard
  • Ib Jarle Christensen
  • Lars Bastholt
  • Henrik Schmidt
Original Article


Fever is frequently observed in conjunction with interleukin-2 (IL-2)-based immunotherapy. Traditionally, fever has been regarded as an undesirable side effect and treated with fever-lowering drugs. However, new insights in tumor immunology suggest that elevated temperature may facilitate a more effective antitumor immune response. The purpose of this retrospective study was to examine the potential role of the IL-2-induced fever in melanoma patients treated with or without paracetamol in two consecutive cohorts. One hundred and seventy-nine patients with metastatic melanoma treated with a modified decrescendo regimen of IL-2 and Interferon (IFN) between 2004 and 2010 were retrospectively studied. 87 patients treated before 2007 received paracetamol as part of the treatment schedule, and 92 patients treated after 2007 did not receive paracetamol routinely. Body temperature was analyzed as dichotomized and continuous variables and correlated to objective tumor response and overall survival using logistic regression and Cox proportional hazard analysis. Patients experiencing peak temperature of ≥39.5 °C had a median OS of 15.2 months compared to 8.7 months among patients with lower temperatures (P = 0.01). In the multivariate analysis, peak temperature of ≥39.5 °C (HR 0.53; P = 0.026) and high mean temperature (HR 0.56; P = 0.004) were independent prognostic factors for improved survival. We suggest high fever as a biomarker for improved survival in melanoma patients treated with IL-2/IFN. The routine use of fever-reducing drugs during immunotherapy can therefore be questioned. More studies are needed to evaluate the role of fever and the use of antipyretics during cytokine-based immunotherapy.


Melanoma Immunotherapy Fever IL-2 Interferon 



Area under the curve


Confidence interval


Complete response


Computed tomography


Dendritic cells


Hazard ratio


Interferon alpha




Lactate dehydrogenase


Million units


Natural killer cells


Non-steroidal anti-inflammatory drugs


Overall survival


Partial response


WHO performance status


Response criteria for solid tumors


Stable disease


Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Anne Helene Køstner
    • 1
    Email author
  • Mai-Britt Bjørklund Ellegaard
    • 1
  • Ib Jarle Christensen
    • 2
  • Lars Bastholt
    • 3
  • Henrik Schmidt
    • 1
  1. 1.Department of OncologyAarhus University HospitalÅrhusDenmark
  2. 2.The Finsen Laboratory, Rigshospitalet and The Biotech and Research Innovation Center (BRIC)University of CopenhagenCopenhagenDenmark
  3. 3.Department of OncologyOdense University HospitalOdenseDenmark

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