Oral Prednisolone Effect on Cancer WHO Stepladder Analgesia Protocol

Introduction: pain in cancer patients is based on the concept of the World Health Organization (WHO) analgesic ladder and was recently updated with the EAPC (European Association for Palliative Care) recommendations. (1) Cancer pain management using opioids administered alone or in combination with adjuvant analgesics. Spinal cord compression, superior vena cava obstruction, raised intracranial pressure, and bowel obstruction is better established than in other nonspecific indications Corticosteroids adjuvant use for neuropathic and bone pain treatment. However, despite widespread use of corticosteroids, scientific evidence about its efficacy in cancer pain management is limited. According to the cancer Pain Management Index (PMI) (2), approximately one-third of patients do not receive appropriate analgesia proportional to their pain intensity (PI). This protocol aims to clarify pors and cons of interrupted steroid dosing in chronic cancer pain WHO stepladder analgesia protocol.

World Health Organization (WHO) analgesic ladder; Step I recommends non-opioid analgesics for mild pain. Step II specifies the use of weak opioids for moderate pain. Step III comprises the use of strong opioids for severe pain (4). Recently the European Association for Palliative Care (EAPC) recommendations (5, 6). Nociceptive and neuropathic components of cancer pain responsiveness to opioids is necessary to achieve good pain alleviation. Medical data demonstrate that complete pain relief is rarely achieved in cancer patients; nonetheless, it can be significantly reduced (7). However, some authors have suggested eliminating the second step of the analgesic ladder, with weak opioids being replaced with low doses of oral morphine (8, 9).

Inadequate assessment leads to inadequate management of cancer pain. Brief Pain Inventory (PI), a pain assessment tool that measures both the intensity of the pain (sensory dimension) and the interference of cancer pain in the patient's life (reactive dimension). It also queries the patient about pain relief, pain quality, and patient perception of the cause of pain. (10) The Pain Management Index (PMI) is widely used in the assessment of pain management, and negative scores are traditionally considered to indicate inadequate pain management. PMI scores are inversely associated with the proportion of patients with pain interference (PI). However, PMI scores of - 1 do not always indicate inadequate pain management; pain management should, therefore, be evaluated from multiple perspectives.

Hypothalamic-pituitary-Adrenal Axis (HPA) axis, sudden cessation of corticosteroid therapy may result in adrenal failure. Clinically significant HPA axis suppression is rare if a steroid is administered for less than 3 weeks (11). Steroid withdrawal syndromes: Relapse of the disease, symptoms of steroid withdrawal syndrome such as lethargy, depression, anorexia, nausea, myalgia, or arthralgia (12). Steroid Tapering: The most suitable method of tapering has not been established as yet. After the glucocorticoid withdrawal, the hypothalamic and pituitary functions recover first, followed by the adrenocortical function. Full recovery of adrenal function can take months, or even up to a year (13), especially after prolonged steroid treatment with high doses. A possible scheme of steroid discontinuation is Prednisolone or equivalent daily dose≥ 7.5 mg reduce rapidly 2.5 mg every 3-4 days, then 5-7.5 mg reduce by 1 mg every 2-4 weeks, then < 5 mg Reduce by 1 mg every 2-4 weeks (13).

Prednisolone relative biologic potencies are; Salt retention 0.75, Anti-inflammatory effect 3, and HPA axis suppression 4. Nociception consists of four stages: Transduction (in peripheral nociceptors), transmission (via neurons), modulation, and pain perception. The possible role of steroids on every step of remain unclear; Reduction in inflammation decreases nociceptors activation (14) , inhibit the expression of collagenase, reduce pro-inflammatory cytokines, stimulate the synthesis of lipocortin (15), reduction of peritumoral edema leads to the improvement in analgesia in brain metastases (16) and spinal cord compression (17) , Decrease of spontaneous discharge \& reduce neuropathic pain, Modulate neural activity and plasticity. There has been little evidence for this in the literature with cancer-induced pain, nausea, and vomiting, fatigue, cancer-induced anorexia-cachexia, depressed mood, or poor general well-being and dyspnea. (18)