Neoplastic Fever

Neoplastic fever, that is fever arising solely as a manifestation of malignancy, is not as common as was thought but still constitutes a troublesome symptom and is difficult to manage. The mechanism of neoplastic fever production involves cytokines such as tumour necrosis factor (TNF), interleukins 1 and 6 (IL-I, IL-6) and interferon (IFN), produced either by host macrophages in response to tumour, or sometimes by the tumour itself. The cytokines stimulate production of prostaglandins which act on the hypothalamus causing a change in the thermostatic set point. This mechanism is similar to that of infective fever. Paracetamol (acetaminophen) will often only partially lyse neoplastic fever but nonsteroidal anti-inflammatory drugs have been shown to be effective. On the basis of small studies, naproxen has been proposed as a useful test to discriminate between neoplastic and infective fever. If this is so, it must be acting through a pathway hitherto undescribed and specific to neoplastic fever. Other work shows that this group of drugs effectively lyses both types of fever. Therefore larger studies are needed to confirm or refute the “Naproxen test” and neoplastic fever remains a diagnosis of exclusion. In the future, cytokine antagonists may have a role in managing neoplastic fever, but, until their actions are better understood, nonsteroidal anti-inflammatory drugs remain the medication of choice if standard antipyretics have failed.