Information ⬇
Editors
Pharmacological Treatment of Cancer Pain
Essentials
- Therapies that are effective against the cancer itself, such as antineoplastic agents, radiotherapy and surgery, often also relieve pain efficiently. If these treatments are not sufficient alone or if they cannot be used, pain is managed with medications or regional anaesthesia. Psychosocial support is an essential part of cancer pain management.
- A stepwise approach to treatment methods in comprehensive cancer pain management is presented in picture .
- Treatment is started with a NSAID or with paracetamol, unless these are contraindicated.
- An opioid is added when the pain becomes more severe (and the ensuing constipation and other adverse effects are treated as well).
- Pain induced by nerve damage is treated with tricyclic antidepressants or SNRIs and/or gabapentinoids (gabapentin and pregabalin).
Principles
- The principles of pain management
- Effectiveness
- Feasibility
- Continuous pain relief at a stable dose by using a sustained-release drug
- Management of pain peaks with a rapid-acting drug
- Minimization of adverse effects by changing the opioid or route of administration or by managing them with suitable drugs
- Regular follow-up of the therapy
- Pain assessment
- Is pain relieved with the prescribed drug and dose? If it does not:
- Has the patient taken / been given the prescribed drugs?
- If not, why (fears, adverse effects)?
- Is the drug absorbed? Does another drug inhibit the effect of the analgesic drug?
- NSAIDs are more effective than paracetamol in pain relief.
- The efficacy of different NSAIDs in the management of cancer pain has not been compared. In the range of recommended doses, a clear dose-response has been shown for various NSAIDs (better pain relief with higher doses).
- Adverse effects to be considered include hypersensitivity and effects on gastric mucosa, platelet function, renal circulation and heart function.
- During treatment with some cytotoxic drugs (e.g. methotrexate) only paracetamol is safe to use.
- Gastric irritation can be alleviated with sucralfate, H2 antagonists, proton pump inhibitors (omeprazole, lansoprazole and pantoprazole), and with a prostaglandin E1 analogue (misoprostole).
- Selective COX-2 inhibitors (coxibs) cause less GI damage and do not prevent thrombocyte aggregation compared with traditional NSAIDs. As to renal function, they have no advantage over other NSAIDs. Coxibs are not recommended for patients who have an increased risk of myocardial infarction Safe Use of Non-Steroidal Anti-Inflammatory Drugs (Nsaids). As regards pain relief, selective COX-2 inhibitors do not provide any additional benefit except for their long duration of action. Inhibition of COX-2 may inhibit the growth of cancer cells.
- Different NSAIDs should not be administered simultaneously. If the drug is not efficient alone, an opioid should be combined with it.
- An NSAID should be continued with the opioid if it has been beneficial as these two drugs with different modes of action usually give better pain relief when they are combined. NSAIDs are particularly effective for pain caused by skeletal metastases.
Opioids
- Severity of pain determines which opioid should be used. Opioids can be classified into three groups on the basis of their efficacy and ceiling effect:
- Weak opioids
- Codeine (only in combination products) and tramadol. Both are prodrugs that require a functional CYP2D6 enzyme in order to function as opioids.
- Medium-strength opioids
- Strong opioids (in alphabetical order)
- Interindividual differences in adverse effects and efficacy may be significant. If an adequate dose of one opioid is not effective, change to another.
- Morphine is still considered as the first-line strong opioid for oral administration. In Finland, however, oxycodone has replaced morphine as the most used strong opioid.
- Combined sustained-release tablets containing oxycodone and naloxone are available (naloxone is an opioid antagonist which is metabolized in the liver, but in the gut it prevents constipation caused by oxycodone). Different strengths exist, but the ratio is always 2:1 (e.g. 5 mg oxycodone, 2.5 mg naloxone).
- Opioids very rarely cause psychological dependence in cancer patients.
- Because of neuroadaptation (physiological dependence) sudden discontinuation of opioid medication leads to withdrawal symptoms (this is not psychological dependence). Therefore, opioids should not be discontinued abruptly.
- If the pain is opioid-sensitive (alleviated with opioids), the effect will not necessarily wear off even if the patient uses the drug for several years. The effect may wear off, in which case the dosage needs to be increased. Changing the opioid to another opioid may increase the effect. The opioid dosage should not be increased, however, without considering the reasons behind the increased pain (severe mental anxiety, for example). High opioid doses may increase pain sensitivity (hyperalgesia). Other adverse effects also occur more frequently with higher dosage.
- Need for opioids may increase as the disease progresses and pains become more intense, as an effect of other drugs or due to the development of tolerance.
Constant pain relief and treatment of pain peaks
- Morphine, oxycodone and hydromorphone are available as sustained-release tablets that are administered twice daily. The effect of sustained-release preparations begins within one to two hours.
- Breakthrough pain requires rapid relief, which is achieved with morphine or oxycodone solution or with normal release oxycodone tablets. The additional dose for breakthrough pain is one sixth of the normal daily dose of the corresponding preparation. The fastest pain relief can be achieved by transmucosal fentanyl, especially as nasal spray.
Avoid intramuscular injections!
- Oral opioids are a more simple and humane option compared with intramuscular injections; a terminal-phase patient has little muscle tissue left, injections are painful and have to be repeated at 2-4-h intervals. A patient in poor condition has trouble learning to pull a small amount of the drug into the syringe and to inject it oneself.
- Oral administration of a liquid opioid is as effective as i.m. administration, as long as the dose is sufficient.
Subcutaneous infusion
- If the patient cannot take oral medication because of a GI obstruction or severe nausea, constant pain relief can be achieved with subcutaneous infusion. Both morphine (1/3 of the daily oral dose) and oxycodone (1/2 of the daily oral dose) can be given as a subcutaneous infusion.
- As an alternative to subcutaneous infusion, a paediatric Viggo® cannula can be inserted subcutaneously and the drug is administered through it by boluses. This technique is used in hospital-at-home settings and also a lay caregiver can administer the drug.
- An antiemetic can be administered concomitantly with the opioid infusion (haloperidol 2-5 mg/day).
- Transdermal fentanyl administered through a matrix membrane patch is an alternative to subcutaneous infusion. The patch is changed every 72 hours (table T1).
Dose of transdermal fentanyl
Oral dose of morphine (mg/24h)* | Dose of transdermal fentanyl (µg/h) |
---|
<135 | 25 |
135-224 | 50 |
225-314 | 75 |
315-404 | 100 |
Evidence Summaries ⬆