Dr. Mahay is a clinical oncology/hematology pharmacist at Banner Desert Medical Center in Mesa, Arizona.
Cancer pain continues to be a health care problem due to its growing rate and the continuous undertreatment of patients with cancer pain. Approximately 25% to 40% of patients with newly diagnosed cancers have pain 40% to 70% of the time during treatment and 70% of the time to 90% during advanced stages.
A major fear of cancer patients is associated pain. Cancer can spread by direct invasion or metastasis (bone invasion and/or spinal cord compression). Chemotherapy drugs such as the vinca alkaloids or radiation therapy can produce neuropathic pain, mucositis, hemorrhagic cystitis, phlebitis, and skin burns. Steroids used for the treatment of cancer have been associated with avascular necrosis of the hip and subsequent fracture. Procedures such as venipuncture, bone marrow and tissue biopsy, lumbar puncture, and endoscopic procedures can result in pain and discomfort. Postsurgical pain also may occur in patients who have had a thoracotomy, mastectomy, or amputation to manage their disease.1-3
The first step in treatment is a thorough assessment of the patient's pain, type of cancer, concurrent medical problems, psychosocial status, and environmental factors. The evaluation of the cancer pain includes the description of its location, intensity, and description. Pain intensity can be measured by a standardized written or verbal numerical scale. Other standards of measurement include the radiation of pain, its quality, the onset and temporal pattern, and precipitating and palliating factors.2-4
The oncologic as well as medical history also will help identify sources of pain. Psychosocial and environmental factors can be a source of distress in patients.
Cancer patients need to be reassessed frequently and repeatedly. Pain can increase or change location due to disease progression, cancer-related therapy, concurrent medical conditions, and psychosocial status. These changes can alter the response to analgesic and opioid therapy and require modifications in treatment goals and prognosis.
The World Health Organization (WHO) has established the WHO stepladder approach for the treatment of cancer pain. The ladder starts with nonopioids (acetaminophen and nonsteroidal antiinflammatory drugs [NSAIDs]) followed, as needed, by the addition of mild opioids (eg, codeine). If pain persists, stronger opioids are added and titrated to pain relief. Around-the-clock dosing schedules are used over "on-demand" schedules to minimize the frequent use of medications for breakthrough pain when pain is constant. The use of adjuvant medications and interventional therapies also is recommended when appropriate. This approach to pain management has been said to achieve analgesia in 80% to 90% of cancer patients.1,5,6
NSAIDs and acetaminophen are widely used analgesics. Acetaminophen is the least toxic of these drugs but should be limited to 4 g/day to prevent chronic liver toxicity.2,4 The main use of NSAIDs for cancer pain is for mild pain in opioid-na?ve patients or as co-analgesic therapy of metastatic bone pain and postoperative pain. Caution should be taken in patients at high risk of gastrointestinal or renal toxicity of NSAIDs, who include the elderly, patients with a history of peptic ulcer disease, renal disease, or concomitant use of other nephrotoxic medications.2,4
Opioids are the foundation of drug therapy for cancer pain.1,3-5 Opioids commonly used for mild-to-moderate pain include codeine, hydrocodone, and oxycodone. They are given alone or in combination with an NSAID or acetaminophen.
Opioids frequently used for the relief of severe cancer pain include morphine, oxycodone, hydromorphone, and fentanyl. These agents are comparable in their speed of onset, duration of effect, and side effects. A faster onset and longer duration are achieved by changing the route of administration or formulation. It is not possible to predict how a patient will react to a specific opioid. Individual differences between these drugs can only be recognized by therapeutic trial.4
A fast onset is desired in cases of acute severe pain or when the medication is delivered on an as needed basis. The intravenous (IV) route is the fastest (2 min), followed by intramuscular and subcutaneous administration (20-30 min).2,4 The preferred route is the least invasive. Most patients can use oral opioids for the management of acute and chronic pain. Morphine and oxycodone are available as both oral, 4-hour immediate-release and 12-hour extended-release formulations. At some point during their illness, however, patients will be unable to take oral opioids. In these cases, the opioid can be given by IV or subcutaneous continuous infusion.
Transdermal fentanyl, another option for treatment of pain in cancer patients, is most useful in chronic cancer pain patients who cannot take oral medications or who have shown unmanageable side effects from morphine, oxycodone, or hydromorphone. Buccal fentanyl has been shown to be valuable for immediate-release breakthrough pain in patients using transdermal fentanyl who have adverse effects from other opioids.2-4
More invasive routes, including epidural and intrathecal, are reserved for specific cases where systemic analgesics have failed to relieve pain and caused immense toxicity.2
Adjuvant medications have a primary indication different from pain but enhance the analgesic efficacy of opioids and produce analgesia for specific types of pain. Types of pain most often treated with adjuvant therapy include bone metastases, nerve compression, nerve damage, and visceral distention. The agents used to treat these types of pain include NSAIDs, corticosteroids, tricyclic antidepressants, and anticonvulsants.1,2-4,7
As mentioned previously, NSAIDs such as ibuprofen can be of use in the treatment of inflammatory pain from bone metastases, soft-tissue infiltration, and recent surgery. Ketorolac, when limited to a 5-day course, can be beneficial in patients requiring analgesia who cannot take oral medications.1,2-4,7
Anticonvulsants are used primarily for neuropathic pain. Gabapentin is the most widely used in this class. It has been shown to improve pain control in patients already on opioids and may aid in reduction of the opioid dose. Other agents in this class that can be used for the treatment of neuropathic pain include carbamazepine, phenytoin, and valproic acid, which are limited due to their untoward side effects. Pregabalin and levetiracetam are similar to gabapentin and both have proven efficacy for neuropathic pain.1,2-4,7
Corticosteroids are helpful with pain due to nerve compression, visceral distention, increased intracranial pressure, and soft-tissue infiltration. Short, tapering courses of drugs given in initially high doses are advised to optimize benefits and minimize long-term side effects.1,2-4,6,7 Bone pain can be managed with radiotherapy, as well as agents such as bisphosphonates, pamidronate, and zolendronic acid. In addition, the bisphosphonates decrease pathological skeletal fractures, spinal cord compression, and hypercalcemia.1,2-4,7
Nonpharmacologic interventions such as meditation, hypnosis, music therapy, acupuncture, and massage also can be valuable in the reduction of cancer pain, as well as easing anxiety in cancer patients.8
Pain is a common symptom in patients with cancer of all stages, and pain management is an important goal in these patients. In order to achieve adequate pain control, a comprehensive pain assessment needs to be performed.