Pain Management: Important Goal in Treating Cancer Patients

Dr. Mahay is a clinical oncology/hematologypharmacist at Banner DesertMedical Center in Mesa, Arizona.

Cancer pain continues to be ahealth care problem due to itsgrowing rate and the continuousundertreatment of patients with cancerpain. Approximately 25% to 40% ofpatients with newly diagnosed cancershave pain 40% to 70% of the time duringtreatment and 70% of the time to 90%during advanced stages.

A major fear of cancer patients isassociated pain. Cancer can spreadby direct invasion or metastasis (boneinvasion and/or spinal cord compression).Chemotherapy drugs such as thevinca alkaloids or radiation therapy canproduce neuropathic pain, mucositis,hemorrhagic cystitis, phlebitis, and skinburns. Steroids used for the treatmentof cancer have been associated withavascular necrosis of the hip and subsequentfracture. Procedures such asvenipuncture, bone marrow and tissuebiopsy, lumbar puncture, and endoscopicprocedures can result in painand discomfort. Postsurgical pain alsomay occur in patients who have had athoracotomy, mastectomy, or amputationto manage their disease.^1-3

The first step in treatment is a thoroughassessment of the patient's pain, type ofcancer, concurrent medical problems,psychosocial status, and environmentalfactors. The evaluation of the cancer painincludes the description of its location,intensity, and description. Pain intensitycan be measured by a standardizedwritten or verbal numerical scale. Otherstandards of measurement include theradiation of pain, its quality, the onsetand temporal pattern, and precipitatingand palliating factors.^2-4

The oncologic as well as medical historyalso will help identify sources of pain.Psychosocial and environmental factorscan be a source of distress in patients.

Cancer patients need to be reassessedfrequently and repeatedly. Pain can increaseor change location due to diseaseprogression, cancer-related therapy,concurrent medical conditions, andpsychosocial status. These changes canalter the response to analgesic and opioidtherapy and require modifications intreatment goals and prognosis.

Pain Management

The World Health Organization (WHO)has established the WHO stepladderapproach for the treatment of cancerpain. The ladder starts with nonopioids(acetaminophen and nonsteroidal antiinflammatorydrugs [NSAIDs]) followed,as needed, by the addition of mild opioids(eg, codeine). If pain persists, strongeropioids are added and titrated to painrelief. Around-the-clock dosing schedulesare used over "on-demand"schedules to minimize thefrequent use of medicationsfor breakthrough pain whenpain is constant. The use ofadjuvant medications and interventionaltherapies also isrecommended when appropriate.This approach to painmanagement has been saidto achieve analgesia in 80% to90% of cancer patients.^1,5,6

Nonopioid Analgesics

NSAIDs and acetaminophen are widelyused analgesics. Acetaminophen is theleast toxic of these drugs but should belimited to 4 g/day to prevent chronic livertoxicity.^2,4 The main use of NSAIDs forcancer pain is for mild pain in opioid-na?vepatients or as co-analgesic therapy ofmetastatic bone pain and postoperativepain. Caution should be taken in patientsat high risk of gastrointestinal or renaltoxicity of NSAIDs, who include the elderly,patients with a history of peptic ulcerdisease, renal disease, or concomitantuse of other nephrotoxic medications.^2,4

Opioids

Opioids are the foundation of drug therapyfor cancer pain.^1,3-5 Opioids commonlyused for mild-to-moderate pain includecodeine, hydrocodone, and oxycodone.They are given alone or in combinationwith an NSAID or acetaminophen.

Opioids frequently used for the reliefof severe cancer pain include morphine,oxycodone, hydromorphone, and fentanyl.These agents are comparable in theirspeed of onset, duration of effect, andside effects. A faster onset and longerduration are achieved by changing theroute of administration or formulation. Itis not possible to predict how a patientwill react to a specific opioid. Individualdifferences between these drugs canonly be recognized by therapeutic trial.⁴

A fast onset is desired in cases of acutesevere pain or when the medication isdelivered on an as needed basis. Theintravenous(IV) route is the fastest (2min), followed by intramuscular and subcutaneousadministration (20-30 min).^2,4The preferred route is the least invasive.Most patients can use oral opioids forthe management of acute and chronicpain. Morphine and oxycodone are availableas both oral, 4-hour immediate-releaseand 12-hour extended-releaseformulations. At some point during their illness, however, patientswill be unable to take oral opioids. In these cases, the opioid canbe given by IV or subcutaneous continuous infusion.

Transdermal fentanyl, another option for treatment of pain incancer patients, is most useful in chronic cancer pain patientswho cannot take oral medications or who have shown unmanageableside effects from morphine, oxycodone, or hydromorphone.Buccal fentanyl has been shown to be valuable for immediate-releasebreakthrough pain in patients using transdermal fentanylwho have adverse effects from other opioids.^2-4

More invasive routes, including epidural and intrathecal, arereserved for specific cases where systemic analgesics havefailed to relieve pain and caused immense toxicity.²

Adjuvants

Adjuvant medications have a primary indication different frompain but enhance the analgesic efficacy of opioids and produceanalgesia for specific types of pain. Types of pain mostoften treated with adjuvant therapy include bone metastases,nerve compression, nerve damage, and visceral distention. Theagents used to treat these types of pain include NSAIDs, corticosteroids,tricyclic antidepressants, and anticonvulsants.^1,2-4,7

NSAIDs

As mentioned previously, NSAIDs such as ibuprofen can be ofuse 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 patientsrequiring analgesia who cannot take oral medications.^1,2-4,7

Anticonvulsants

Anticonvulsants are used primarily for neuropathic pain.Gabapentin is the most widely used in this class. It has beenshown to improve pain control in patients already on opioidsand may aid in reduction of the opioid dose. Other agentsin this class that can be used for the treatment of neuropathicpain include carbamazepine, phenytoin, and valproicacid, which are limited due to their untoward side effects.Pregabalin and levetiracetam are similar to gabapentin andboth have proven efficacy for neuropathic pain.^1,2-4,7

Corticosteroids

Corticosteroids are helpful with pain due to nerve compression,visceral distention, increased intracranial pressure, andsoft-tissue infiltration. Short, tapering courses of drugs givenin initially high doses are advised to optimize benefits andminimize long-term side effects.^1,2-4,6,7Bone pain can be managed with radiotherapy, as well asagents such as bisphosphonates, pamidronate, and zolendronicacid. In addition, the bisphosphonates decrease pathological skeletalfractures, spinal cord compression, and hypercalcemia.^1,2-4,7

Nonpharmacologic Options

Nonpharmacologic interventions such as meditation, hypnosis,music therapy, acupuncture, and massage also can bevaluable in the reduction of cancer pain, as well as easinganxiety in cancer patients.⁸

Conclusion

Pain is a common symptom in patients with cancer of allstages, and pain management is an important goal in thesepatients. In order to achieve adequate pain control, a comprehensivepain assessment needs to be performed.

References

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• Caimi P, Cymet TC. As if the cancer wasn't enough! Understanding and treating the pain that comes with cancer. Compr Ther. 2006;32(3):176-181.
• Levy MH, Samuel TA. Management of cancer pain. Semin Oncol. 2005; 32(2):179-193.
• National Comprehensive Cancer Network. Adult Cancer Pain. Clinical Practice Guidelines in Oncology. 2005(2)[online].
• Mercadante S, Fulfaro F. World Health Organization guidelines for cancer pain: a reappraisal. Ann Oncol. 2005;16(suppl 4):iv132-iv135.
• Mcnicol E, Strasseis S, Goudas L, Lau J, Carr D. Nonsteroidal anti-inflammatory drugs, alone or combined with opioids, for cancer pain: a systematic review. J Clin Oncol. 2004;22(10):1975-1992.
• Lussier D, Huskey AG, Portenoy RK. Adjuvant analgesics in cancer pain management. Oncologist. 2004;9(5):571-591.
• Menefee Pujol LA, Monti DA. Managing cancer pain with nonpharmacologic and complementary therapies. J Am Osteopath Assoc. 2007;107(suppl 7):ES15-ES21.