Corticosteroids in oncology: Use, overuse, indications, contraindications.
An Italian Association of Medical Oncology (AIOM)/ Italian Association of Medical Diabetologists (AMD)/ Italian Society of Endocrinology (SIE)/ Italian Society of Pharmacology (SIF) multidisciplinary consensus position paper
 

1. Introduction
Synthetic corticosteroids (CSs) are responsible for multiple activities through genomic and non-genomic effects influencing all cells, tissues, and metabolic processes. CSs are one of the most used drug classes in medicine, particularly in cancer patients due to their ability to interfere with multiple biochemical and cellular processes that play a role in inflammation and immune system regulation (Kalfeist et al., 2022).
The main CSs are hydrocortisone, prednisone, prednisolone, methylprednisolone, and dexamethasone (Table 1). To date, CSs are mainly used as supportive treatment for cancer related complications and anticancer treatments side effects, including nausea and vomiting, brain edema and pain flairs, and to treat or prevent hypersensitivity reactions (Aldea et al., 2020). Diabetes mellitus (DM), poorly controlled arterial hypertension, recent acute coronary syndrome, peptic ulcer disease and osteoporosis represent relative contraindications to the treatment with CSs, although their cautious use could be beneficial even in these conditions. The only absolute contraindication to CSs is represented by active infections not controlled by specific therapy as well as hypersensitivity to any component of the formulation.
A recent alert regards a duality of CSs effects in oncology: the signal starting from CSs receptor activation may result both in tumour suppression and progression, according to the molecular pathway involved in the tumourigenesis (Mayayo-Peralta et al., 2021). A specific point concerns CSs and immunotherapy in cancer patients with autoimmune side effects; it has been supposed that CSs can potentially reduce anti-tumour immunity induced by immunotherapy against cancer (Gupta et al., 2021). Furthermore, adverse events (AEs) could be related to CSs therapy, mainly including metabolic/endocrinological, gastrointestinal, immunological, and cardiovascular effects. These side effects are generally related to dose and treatment duration, as well as to timing of reduction/ withdrawal of these drugs.
Furthermore, in heavily treated patients the pharmacological interferences can change the consequences to CSs through the modulation of the CYP3A4, the major metabolic pathway of most of the synthetic CSs (Prete and Bancos, 2021).
For these reasons, CSs need to be used with full awareness of their pharmacological properties, modulating type, dose and duration of the therapy according to the indication, tumour type and patient conditions.
In this review, a panel of experts of the Italian Association of Medical Oncology (AIOM)/ Italian Association of Medical Diabetologists (AMD)/ Italian Society of Endocrinology (SIE)/ Italian Society of Pharmacology (SIF) discuss about use and overuse of CSs therapy in oncology, focusing on mechanisms of action and pharmacological characteristics of the available CSs, the current and emerging therapeutic indications and contraindications of CSs in oncology, the side effects.

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