The Role of Corticosteroids in the Treatment of Pain in Cancer PatientsI started getting severe joint pains last Thursday and attributed it to stress because I have a family member who is steroids bone pain hospice and I had to travel by plane to visit her. The pain and frequency continues to increase and has spread from knees dbol results on cycle ankles and hip steroids bone pain bone pain occurring in shins and thighs. I have been on 60 mg of Prednisone since Aug 18th. Also, I have been exposed to 3 people with bad colds when I travelled and now steroids bone pain daughter came down with a bad cold as well on Thurs. Is this a common side effect or can it be a sign of an infection brewing? Thanks for any help, Doreen.
Prednisone Side Effects, Dosage, Uses & Withdrawal Symptoms
Pain is one of the most frequent and most distressing symptoms in the course of cancer. Cancer pain may be relieved effectively with opioids administered alone or in combination with adjuvant analgesics. Corticosteroids are commonly used adjuvant analgesics and play an important role in neuropathic and bone pain treatment.
However, in spite of the common use of corticosteroids, there is limited scientific evidence demonstrating their efficacy in cancer patients with pain.
The use of corticosteroids in spinal cord compression, superior vena cava obstruction, raised intracranial pressure, and bowel obstruction is better established than in other nonspecific indications. This review aims to present the role of steroids in pain and management of other symptoms in cancer patients according to the available data, and discusses practical aspects of steroid use.
The management of this symptom is generally based on the concept of the World Health Organization WHO analgesic ladder. This three-step framework was published for the first time in by the WHO to promote rational use of analgesic medications in the treatment of cancer pain. Step I recommends nonopioid 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 [ 1 ]. The knowledge of both basic types of pain nociceptive and neuropathic and their 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 [ 4 ]. To achieve better pain relief, apart from the use of the analgesics recommended by the WHO ladder, an appropriate application of adjuvant analgesics i. Certain data confirm some of the generally known rules, which are presented below.
In patients with bone pain, opioids may be combined with nonsteroidal anti-inflammatory drugs NSAIDs and bisphosphonates along with local or systemic radiotherapy [ 7 ]. Neuropathic pain apart from opioid analgesics may require antidepressants, anticonvulsants, and local anesthetics. In patients with very severe neuropathic pain, the combination of opioids and N -methyl- D -aspartate receptor NMDA antagonists, namely ketamine, is recommended [ 8 ].
Patients with visceral, colicky pain, especially in the course of bowel obstruction, should be treated with opioid analgesics and spasmolytics such as hyoscine butylbromide, hyoscine hydrobromide, or glycopyrrolate [ 9 ].
Steroids can reduce pain intensity by inhibiting prostaglandin synthesis and reducing vascular permeability. Their role in controlling cancer pain and other indications in the course of cancer and some practical aspects of steroid use will be discussed in this article. According to the WHO and EAPC pain management recommendations, an adjuvant pain medication should be considered at each step of the WHO analgesic ladder, especially when the anti-inflammatory effect is needed.
Endogenous steroids, depending on their nature, site of synthesis, and specific clinical features, can be divided into four groups: Generally, steroids are produced in the adrenals and gonads, and some other tissues such as the bowel, liver, prostate, and nervous system neurosteroids may synthesize or metabolize them [ 10 ]. Corticosteroids have a wide range of actions. The knowledge of different corticosteroid properties is an important factor in the therapeutic decision making process. The principal sites of action of glucocorticoids in humans and some clinical consequences of its excess.
Adapted and modified from Stewart [ 11 ]. The anti-inflammatory effect and vascular permeability reduction are the clinical results of steroid use. Because the mineralocorticoid properties of steroids may lead to a higher risk of sodium excess, potassium loss, and water retention in such cases, a concurrent supplementation of potassium should be considered , cortisone or hydrocortisone are rarely employed for long-term anti-inflammatory therapy due to the highest sodium-retaining potency.
The negative feedback of the HPA axis by endogenous and synthetic steroids is well established. It is a dose- and time-dependent process. Consequently, a sudden cessation of corticosteroid therapy may result in adrenal failure. Such patients can withdraw from steroids suddenly, with no harmful effects [ 11 ].
There are some clinical situations i. Various syndromes may occur when the glucocorticoid is withdrawn or reduced. The first is relapse of the disease for which the steroids were prescribed. The second is a combination of nonspecific symptoms of steroid withdrawal syndrome i. This syndrome must be distinguished from the suppressed HPA axis or relapse of the underlying disease.
The third syndrome is acute adrenal insufficiency, which could be precipitated by surgery, intercurrent disease, or stress and may result in a hemodynamic collapse [ 12 ]. Clinicians are often unsure how to safely reduce the dose of steroids. 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. Adapted and modified from Livanou et al. The process of pain origination is called nociception. It consists of four stages: The possible role of steroids on every step of nociception has been raised even though the exact mechanisms remain unclear.
This process leads to an increase in pain perception. The reduction in inflammation involved in this process decreases nociceptors activation, and thus, can diminish pain intensity. A decrease in pathological electrical activity of damaged neurons is also suggested [ 14 ]. The anti-inflammatory effect of glucocorticosteroids results from their ability to inhibit the expression of collagenase the key enzyme involved in tissue degeneration during inflammatory mechanisms , reduce pro-inflammatory cytokines, and stimulate the synthesis of lipocortin blocks the production of eicosanoids [ 15 ].
As a consequence, corticosteroids are considered to be the most effective strategy against inflammatory pain. Steroids also have an anti-swelling effect. The reduction of peritumoral edema by the shrinkage of tumor in response to steroid therapy may lead to the improvement in analgesia in brain metastases [ 16 ] and spinal cord compression [ 17 ].
The modulation of neuroimmune interactions by corticosteroids and the decrease of spontaneous discharge in an injured nerve may reduce neuropathic pain. The receptors of various steroid hormones are expressed in several neural structures, allowing steroids to control the development, growth, maturation, differentiation, and plasticity of the CNS and PNS.
By modulating neural activity and plasticity, the steroids are suspected to play an important role in pain sensation. Sex steroids androgens and estrogens are key factors accounting for the gender difference in pain and analgesia.
Androgens, particularly testosterone, exert an analgesic effect in humans while estrogens were found to have both the hyperalgesic and analgesic effects, depending on the experimental conditions [ 19 , 20 ]. The most often prescribed corticosteroid for pain treatment is dexamethasone. Long-acting dexamethasone causes less fluid retention than other steroids because it has less mineralocorticoid effect. However, betamethasone equipotent to dexamethasone , prednisone, and prednisolone also may be used [ 22 ].
Dexamethasone is metabolized by the hepatic enzyme CYP3A4 [ 23 ], and like other drugs metabolized in this way, it has numerous potential interactions.
It may affect the metabolism of carbamazepine, tricyclic antidepressants, venlafaxine, dextromethorphan, and, to less extent, methadone.
Corticosteroids are commonly prescribed in cancer patients for a variety of symptoms [ 24 , 25 ]. These include some specific and non-specific indications. There is evidence for the use of corticosteroids for specific indications such as raised intracranial pressure, spinal cord compression, superior vena cava obstruction, and bowel obstruction.
However, there has been little evidence for this in the literature with regard to hypercalcemia and nonspecific indications such as pain, nausea and vomiting, fatigue, cancer-induced anorexia-cachexia, depressed mood, or poor general well-being and dyspnea [ 26 ].
Adapted and modified from Exton [ 26 ]. Corticosteroids display short- and long-term toxicities. The immediate adverse effects include immunosuppression, which may manifest as candidosis, hyperglycemia, and psychiatric disorders. Therefore, due to a wide range of adverse effects, the lowest effective dose should be used. Additionally, other medications to counteract steroid side effects can be prescribed. The combination of NSAIDs and steroids increases the risk of gastric bleeding fold; therefore, it should be avoided or gastroprotective drugs ought to be administered concurrently [ 27 ].
Bisphosphonates should be considered in the case of elderly patients and patients at risk of osteoporosis, especially when chronic steroid therapy is intended.
Due to the diabetogenic effect of steroids, regular measurements of glucose levels are needed in these patients as well. All patients should be reviewed regularly to ensure that the treatment benefits outweigh the risks [ 7 ].
In an uncontrolled study, oral candidosis and proximal myopathy were the most frequent adverse effects attributable to steroid therapy. The most common reason for discontinuation of dexamethasone treatment was death or general deterioration.
Although hiccup is not a very frequent adverse effect of dexamethasone, in a recent case series, Kang et al.
Dexamethasone is often administered subcutaneously. It is alkaline, so it is highly likely to be incompatible with acidic solutions. If dexamethasone is to be mixed with other drugs, as much diluents as possible should be added before the addition of dexamethasone. Dexamethasone is incompatible in mixtures with haloperidol, midazolam, promethazine, and levomepromazine.
Glycopyrronium chemically interacts with dexamethasone, but no precipitate forms; therefore, this combination should be avoided. Dexamethasone is compatible in mixtures with morphine, diamorphine, oxycodone, fentanyl, alfentanil, hydromorphone, dihydrocodeine, tramadol, hyoscine butylbromide, hyoscine hydrobromide, metoclopramide, and ondansetron [ 31 ].
There is little recent evidence for the effectiveness and toxicity of corticosteroids in cancer. Some uncontrolled studies reported benefits of corticosteroids on pain and symptom control in these patients.
The issue of an appropriate steroid treatment is discussed in the literature, and many questions regarding this problem have been raised What are the exact indications for corticosteroid use? When should the steroid treatment be started? How long are steroids effective in symptom management, including pain? What is the most effective steroid dose?
What are the most common adverse effects in cancer patients? Do we prescribe steroids too often in palliative care? The studies presented below attempted to answer these important queries.
Corticosteroids were prescribed to Younger patients were treated more often with corticosteroids [ 32 ]. A retrospective observation of corticosteroid use at the end of life in hospice patients conducted by Gannon et al.