martes, 6 de septiembre de 2016

Cancer Pain (PDQ®)—Health Professional Version - National Cancer Institute

Cancer Pain (PDQ®)—Health Professional Version - National Cancer Institute

National Cancer Institute

Cancer Pain (PDQ®)–Health Professional Version


General Information About Cancer Pain

Pain is one of the most common symptoms in cancer patients and often has a negative impact on patients’ functional status and quality of life. The goal of the following summary is to provide evidence-based, up-to-date, and practical information on the management of cancer pain.
Effective pain management can generally be accomplished by paying attention to the following steps:[1]
  1. Regular screening to ensure that the patient’s pain is recognized early. (Refer to thePain Assessment section of this summary for more information.)
  2. Proper characterization of the pain to identify underlying pathophysiology, which could significantly influence treatment options. (Refer to the Pain Classificationsection of this summary for more information).
    • Is the pain acute or chronic?
    • Is it secondary to cancer, cancer treatment, other causes, or a combination?
    • Is it somatic, visceral, neuropathic, or mixed?
    • Is there an incidental component?
    • Is there breakthrough pain?
  3. Determining whether the pain requires pharmacologic and/or other modalities of treatment. Pain is often multifactorial in nature, so factors that may modulate pain expression, such as psychological distress and substance use, should be assessed. (Refer to the Background and Definitions section of this summary for more information.)
    • What is the impact of pain on the patient?
    • Is the benefit of treatment likely going to outweigh the risks?
  4. Identifying the optimal pharmacologic and nonpharmacologic treatment options (refer to the Pharmacologic Therapies for Pain Control section of this summary for more information), including referrals to specialists, if needed. (Refer to theModalities for Pain Control: Other Approaches section of this summary for more information.) Complex pain often requires multidimensional interdisciplinary evaluation and intervention. There are many issues to consider when determining the most appropriate treatment, such as the following:
    • Previous pain treatments.
    • Patient prognosis.
    • Predictive factors for pain control (e.g., psychological distress).
    • Impact on function.
    • Comorbidities (e.g., renal or hepatic failure).
    • Risk of misuse of or addiction to pain medications.
    • Patient preference.
  5. Providing proper education about treatment, including medication administration, expected side effects and associated treatments, and when patients can expect improvement. If opioids are considered, opioid phobia and the risks of opioid use and misuse should be addressed. Patients and family caregivers should be educated about the safe storage, use, and disposal of opioids. One study demonstrated that improper use, storage, and disposal are common among cancer outpatients.[2]
  6. Monitoring the patient longitudinally with return visits to titrate/adjust treatments. Patients with cancer or noncancer pain requiring chronic therapy are monitored closely to optimize treatment and to minimize the likelihood of complications of opioid use, including misuse or abuse. The risks and benefits of opioid use are evaluated regularly, and physician impressions are discussed openly with the patient.

Background and Definitions

The International Association for the Study of Pain defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”[3] Pain is commonly experienced by cancer patients. Its proper assessment requires measuring pain intensity; clarifying the impact of pain on patients’ psychological, social, spiritual, and existential domains; and establishing treatment adherence and responsiveness.
A commonly used approach to pain management employs the World Health Organization (WHO) pain relief ladder, which categorizes pain intensity according to severity and recommends analgesic agents based on their strength.[4] Pain intensity is often assessed using a numeric rating scale (NRS) of 0 to 10. On this scale, 0 indicates no pain, 1 to 3 indicates mild pain, 4 to 6 indicates moderate pain, and 7 to 10 indicates severe pain.[5]
Step 1 on the WHO pain relief ladder treats mild pain. Patients in this category receive nonopioid analgesics such as acetaminophen, nonsteroidal anti-inflammatory drugs, or an adjuvant analgesic, if necessary. Step 2 treats patients experiencing mild to moderate pain who are already taking a nonopioid analgesic, with or without an adjuvant analgesic, but who are still experiencing poor analgesia. Step 2 agents include tramadol and acetaminophen products containing hydrocodone, oxycodone, and codeine. Step 3 treats moderate to severe pain with strong analgesics. Step 3 opioids include morphine, hydromorphone, fentanyl, levorphanol, methadone, oxymorphone, and oxycodone. An open-label randomized trial of low-dose morphine versus weak opioids to treat moderate cancer pain suggests that it is acceptable to bypass weak opioids and go directly to strong opioids (step 3 agents) for patients with moderate cancer pain, as patients randomly assigned to the low-dose morphine arm had more frequent and greater reduction in pain intensity with similarly good tolerability and earlier effect.[6]
Familiarity with opioid pharmacokinetics, equianalgesic dosing, and adverse effects is necessary for their safe and effective use. The appropriate use of adjuvant pharmacological and nonpharmacological interventions is needed to optimize pain management.


Pain occurs in 20% to 50% of patients with cancer.[7] Roughly 80% of patients with advanced-stage cancer have moderate to severe pain.[8] One meta-analysis looking at pooled data from 52 studies found that more than half of patients had pain.[9] Younger patients are more likely to experience cancer pain and pain flares than are older patients.[10]
Cancer patients often have multiple sites of pain.[11] Patients rated pain from 4 to 6 (severe) on the NRS, with exacerbations rated as high as 7.

Causes of Cancer Pain: Cancer, Cancer Treatments, and Comorbidities

A study evaluating the characteristics of patients (N = 100) with advanced cancer presenting to a palliative care service found the primary tumor as the chief cause of pain in 68% of patients.[11] Most pain was somatic, and pain was as likely to be continuous as intermittent.
Pain can be caused by cancer therapies, including surgery, radiation therapy, chemotherapy, targeted therapy, supportive care therapies, and/or diagnostic procedures. A systematic review of the literature identified reports of pain occurring in 59% of patients receiving anticancer treatment and in 33% of patients after curative treatments.[12] The prevalence of chronic nonmalignant pain—such as chronic low back pain, osteoarthritis pain, fibromyalgia, and chronic daily headaches—has not been well characterized in cancer patients. It has been reported to be between 2% and 76%, depending on the patient population and how pain was assessed.[13-16]

Infusion-related pain syndromes

The infusion of intravenous chemotherapy causes four pain syndromes: venous spasm, chemical phlebitis, vesicant extravasation, and anthracycline-associated flare.[17-19] Venous spasm is treated by application of a warm compress or decrease in the infusion rate. Chemical phlebitis may result from chemotherapy or nonchemotherapy infusions such as potassium chloride and hyperosmolar solutions.[18] Vesicant extravasation may cause intense pain followed by desquamation and ulceration.[17] Doxorubicin may result in the venous flare reaction, which includes local urticaria, pain, or stinging.[19] Some chemotherapy agents such as vinorelbine may cause pain at the tumor site.[20]

Treatment-related mucositis

Severe mucositis often occurs as a consequence of myeloablative chemotherapy and standard-intensity therapy.[21] Cytotoxic agents commonly associated with mucositis are cytarabine, doxorubicin, etoposide, 5-fluorouracil, and methotrexate. Epidermal growth factor receptor (EGFR) inhibitors, multitargeted tyrosine kinase inhibitors, and mammalian target of rapamycin inhibitors also cause mucositis.[22,23] Risk factors for mucositis include preexisting oral pathology, poor dental hygiene, and younger age.[21]

Chemotherapy-related musculoskeletal pain

Paclitaxel generates a syndrome of diffuse arthralgias and myalgias in 10% to 20% of patients.[24] Diffuse pain in joints and muscles appears 1 to 2 days after the infusion and lasts a median of 4 to 5 days. Pain originates in the back, hips, shoulders, thighs, legs, and feet. Weight bearing, walking, or tactile contact exacerbates the pain. Steroids may reduce the tendency to develop myalgia and arthralgias. Among hormonal therapies, aromatase inhibitors cause musculoskeletal symptoms, osteoporotic fractures, arthralgias, and myalgias.[25]

Dermatologic complications and chemotherapy

EGFR inhibitors cause dermatitis with ensuing pain.[26] Acute herpetic neuralgia occurs with a significantly increased incidence among cancer patients, especially those with hematologic malignancies and those receiving immunosuppressive therapies.[27] The pain usually resolves within 2 months but can persist and become postherpetic neuralgia. The palmar-plantar erythrodysesthesia syndrome is observed in association with continuously infused 5-fluorouracil, capecitabine,[28] liposomal doxorubicin,[29] and paclitaxel.[30] Targeted agents such as sorafenib and sunitinib are also associated with hand-foot–like syndrome.[31] Patients develop tingling or burning in their palms and soles, followed by an erythematous rash. Management often requires discontinuing therapy or reducing the treatment dose.

Supportive care therapies and pain

Supportive care therapies can cause pain, as typified by bisphosphonate-associated osteonecrosis of the jaw.[32] Corticosteroid use has also been associated with the development of avascular necrosis.[33]

Radiation-induced pain

Radiation causes several pain syndromes, including mucositis, mucosal inflammation in areas receiving radiation, pain flares, and radiation dermatitis. Patients may experience pain from brachytherapy and from positioning during treatment (i.e., placement on a radiation treatment table).[34]

Impact on Function and Quality of Life

Cancer pain is associated with increased emotional distress. Both pain duration and pain severity correlate with risk of developing depression. Cancer patients are disabled an average of 12 to 20 days per month, with 28% to 55% unable to work because of their cancer.[35] Cancer survivors may experience distress when their pain unexpectedly persists after completion of cancer treatments.[36] Survivors also experience loss of support from their previous health care team as oncologists transition their care back to primary care providers.
In one study, between 20% and 50% of cancer patients continued to experience pain and functional limitations years posttreatment.[37] Untreated pain leads to requests for physician-assisted suicide.[38] Untreated pain also leads to unnecessary hospital admissions and visits to emergency departments.[39]
  1. Hui D, Bruera E: A personalized approach to assessing and managing pain in patients with cancer. J Clin Oncol 32 (16): 1640-6, 2014. [PUBMED Abstract]
  2. Reddy A, de la Cruz M, Rodriguez EM, et al.: Patterns of storage, use, and disposal of opioids among cancer outpatients. Oncologist 19 (7): 780-5, 2014. [PUBMED Abstract]
  3. Merskey H, Bogduk N, eds.: Classification of Chronic Pain: Description of Chronic Pain Syndromes and Definitions of Pain Terms. 2nd ed. Seattle, Wash: IASP Press, 1994.Also available online. Last accessed June 24, 2016.
  4. Davis MP, Walsh D: Epidemiology of cancer pain and factors influencing poor pain control. Am J Hosp Palliat Care 21 (2): 137-42, 2004 Mar-Apr. [PUBMED Abstract]
  5. Oldenmenger WH, de Raaf PJ, de Klerk C, et al.: Cut points on 0-10 numeric rating scales for symptoms included in the Edmonton Symptom Assessment Scale in cancer patients: a systematic review. J Pain Symptom Manage 45 (6): 1083-93, 2013. [PUBMED Abstract]
  6. Bandieri E, Romero M, Ripamonti CI, et al.: Randomized Trial of Low-Dose Morphine Versus Weak Opioids in Moderate Cancer Pain. J Clin Oncol 34 (5): 436-42, 2016. [PUBMED Abstract]
  7. Fischer DJ, Villines D, Kim YO, et al.: Anxiety, depression, and pain: differences by primary cancer. Support Care Cancer 18 (7): 801-10, 2010. [PUBMED Abstract]
  8. Bruera E, Kim HN: Cancer pain. JAMA 290 (18): 2476-9, 2003. [PUBMED Abstract]
  9. Shaheen PE, Legrand SB, Walsh D, et al.: Errors in opioid prescribing: a prospective survey in cancer pain. J Pain Symptom Manage 39 (4): 702-11, 2010. [PUBMED Abstract]
  10. Green CR, Hart-Johnson T: Cancer pain: an age-based analysis. Pain Med 11 (10): 1525-36, 2010. [PUBMED Abstract]
  11. Gutgsell T, Walsh D, Zhukovsky DS, et al.: A prospective study of the pathophysiology and clinical characteristics of pain in a palliative medicine population. Am J Hosp Palliat Care 20 (2): 140-8, 2003 Mar-Apr. [PUBMED Abstract]
  12. van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, et al.: Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol 18 (9): 1437-49, 2007. [PUBMED Abstract]
  13. Caraceni A, Portenoy RK: An international survey of cancer pain characteristics and syndromes. IASP Task Force on Cancer Pain. International Association for the Study of Pain. Pain 82 (3): 263-74, 1999. [PUBMED Abstract]
  14. Barbera L, Molloy S, Earle CC: Frequency of non-cancer-related pain in patients with cancer. J Clin Oncol 31 (22): 2837, 2013. [PUBMED Abstract]
  15. Childers JW, King LA, Arnold RM: Chronic Pain and Risk Factors for Opioid Misuse in a Palliative Care Clinic. Am J Hosp Palliat Care 32 (6): 654-9, 2015. [PUBMED Abstract]
  16. Massaccesi M, Deodato F, Caravatta L, et al.: Incidence and management of noncancer pain in cancer patients referred to a radiotherapy center. Clin J Pain 29 (11): 944-7, 2013. [PUBMED Abstract]
  17. Sauerland C, Engelking C, Wickham R, et al.: Vesicant extravasation part I: Mechanisms, pathogenesis, and nursing care to reduce risk. Oncol Nurs Forum 33 (6): 1134-41, 2006. [PUBMED Abstract]
  18. Pucino F, Danielson BD, Carlson JD, et al.: Patient tolerance to intravenous potassium chloride with and without lidocaine. Drug Intell Clin Pharm 22 (9): 676-9, 1988. [PUBMED Abstract]
  19. Curran CF, Luce JK, Page JA: Doxorubicin-associated flare reactions. Oncol Nurs Forum 17 (3): 387-9, 1990 May-Jun. [PUBMED Abstract]
  20. Long TD, Twillman RK, Cathers-Schiffman TA, et al.: Treatment of vinorelbine-associated tumor pain. Am J Clin Oncol 24 (4): 414-5, 2001. [PUBMED Abstract]
  21. Peterson DE, Lalla RV: Oral mucositis: the new paradigms. Curr Opin Oncol 22 (4): 318-22, 2010. [PUBMED Abstract]
  22. Lacouture ME, Anadkat MJ, Bensadoun RJ, et al.: Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer 19 (8): 1079-95, 2011. [PUBMED Abstract]
  23. Boers-Doets CB, Epstein JB, Raber-Durlacher JE, et al.: Oral adverse events associated with tyrosine kinase and mammalian target of rapamycin inhibitors in renal cell carcinoma: a structured literature review. Oncologist 17 (1): 135-44, 2012. [PUBMED Abstract]
  24. Loprinzi CL, Maddocks-Christianson K, Wolf SL, et al.: The Paclitaxel acute pain syndrome: sensitization of nociceptors as the putative mechanism. Cancer J 13 (6): 399-403, 2007 Nov-Dec. [PUBMED Abstract]
  25. Coleman RE, Bolten WW, Lansdown M, et al.: Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations. Cancer Treat Rev 34 (3): 275-82, 2008. [PUBMED Abstract]
  26. Lynch TJ Jr, Kim ES, Eaby B, et al.: Epidermal growth factor receptor inhibitor-associated cutaneous toxicities: an evolving paradigm in clinical management. Oncologist 12 (5): 610-21, 2007. [PUBMED Abstract]
  27. Portenoy RK, Duma C, Foley KM: Acute herpetic and postherpetic neuralgia: clinical review and current management. Ann Neurol 20 (6): 651-64, 1986. [PUBMED Abstract]
  28. Gressett SM, Stanford BL, Hardwicke F: Management of hand-foot syndrome induced by capecitabine. J Oncol Pharm Pract 12 (3): 131-41, 2006. [PUBMED Abstract]
  29. Alberts DS, Garcia DJ: Safety aspects of pegylated liposomal doxorubicin in patients with cancer. Drugs 54 (Suppl 4): 30-5, 1997. [PUBMED Abstract]
  30. Vukelja SJ, Baker WJ, Burris HA 3rd, et al.: Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with taxotere. J Natl Cancer Inst 85 (17): 1432-3, 1993. [PUBMED Abstract]
  31. Chu D, Lacouture ME, Fillos T, et al.: Risk of hand-foot skin reaction with sorafenib: a systematic review and meta-analysis. Acta Oncol 47 (2): 176-86, 2008. [PUBMED Abstract]
  32. Prommer EE: Toxicity of bisphosphonates. J Palliat Med 12 (11): 1061-5, 2009. [PUBMED Abstract]
  33. Mattano LA Jr, Devidas M, Nachman JB, et al.: Effect of alternate-week versus continuous dexamethasone scheduling on the risk of osteonecrosis in paediatric patients with acute lymphoblastic leukaemia: results from the CCG-1961 randomised cohort trial. Lancet Oncol 13 (9): 906-15, 2012. [PUBMED Abstract]
  34. Ripamonti CI, Bossi P, Santini D, et al.: Pain related to cancer treatments and diagnostic procedures: a no man's land? Ann Oncol 25 (6): 1097-106, 2014. [PUBMED Abstract]
  35. Brown LF, Kroenke K, Theobald DE, et al.: The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. Psychooncology 19 (7): 734-41, 2010. [PUBMED Abstract]
  36. Jim HS, Andersen BL: Meaning in life mediates the relationship between social and physical functioning and distress in cancer survivors. Br J Health Psychol 12 (Pt 3): 363-81, 2007. [PUBMED Abstract]
  37. Harrington CB, Hansen JA, Moskowitz M, et al.: It's not over when it's over: long-term symptoms in cancer survivors--a systematic review. Int J Psychiatry Med 40 (2): 163-81, 2010. [PUBMED Abstract]
  38. Foley KM: The relationship of pain and symptom management to patient requests for physician-assisted suicide. J Pain Symptom Manage 6 (5): 289-97, 1991. [PUBMED Abstract]
  39. Mayer DK, Travers D, Wyss A, et al.: Why do patients with cancer visit emergency departments? Results of a 2008 population study in North Carolina. J Clin Oncol 29 (19): 2683-8, 2011. [PUBMED Abstract]
  • Updated: August 29, 2016

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