Managing the Pain of Cancer

INTRODUCTION

The word cancer conjures up many frightening and distressing images, death being the most prominent of all. Excruciating pain and horrible side effects are two other common images that spring up at the mention of cancer. It is no mystery why a diagnosis of cancer casts such a broad net of fear and anxiety over a person’s life and the lives of loved ones.

Cancer affects an estimated 82 million Americans. According to the American Cancer Society’s 2004 Cancer Facts and Figures,²³ there are nearly 1.4 million new cancer cases diagnosed annually, with estimated annual deaths just over a half million. Statistically, one out of two men and one out of three women will develop cancer in their lifetimes. Nearly 80% of all cancer diagnoses are made in people aged 55 and older. Childhood cancers are rare. The most common are:²⁴

• Leukemias - (blood cell cancers), approximately 30%, with acute lymphocytic leukemia (ALL) being most common
• Brain and other central nervous system tumors, such as gliomas and medulloblastomas – nearly 20%
• Hodgkins and non-Hodgkins lymphomas – approximately 10% to 15%

Other childhood cancers include bone cancer, neuroblastomas, rhabdomyosarcoma and Wilms tumor in the kidney. Figure 1. lists the incidence of childhood cancers for children up to age 14 in the US for the year ending 2001.

Pain is an extremely prevalent symptom in cancer patients. 30-50% of patients undergoing active cancer treatment experience pain. 70 to 90% of patients with advanced disease states experience moderate to severe pain.²⁵ Despite the availability of analgesics, patients with cancer continue to experience pain.

In a study of 1,308 outpatients with widespread cancer, 42% of those in pain were not given adequate painkillers.²⁶

Cancer studies show that minority patients and the elderly are at increased risk of inadequate analgesics. Consider these study results:

• 40% of elderly residents of U.S. nursing homes with daily pain from cancer didn’t receive any treatment, not even aspirin.²⁷
• Patients treated at centers that predominantly cared for minorities were three times as likely to get inadequate pain control.²⁸

While adequate pain relief can be achieved for up to 90% of cancer patients with relatively simple drug therapies, cancer is often under treated. Medical literature points to a myriad of barriers, some of which include:

• Deficiencies in clinician knowledge about cancer pain assessment and available treatment options
• Tendency for health care providers to put a higher priority on disease control than symptom management
• Patients don’t report pain or don’t comply with pain medications
• System-wide impediments to optimal analgesic therapies (fear of legal sanction, opioid addiction, etc.)

Cancer pain management is also complicated by co-existing conditions. More than 75% of people with cancer have one or more additional chronic conditions; 27.4% have three or more chronic conditions.²⁹

Pain management in the elderly presents further challenges, not only because of a higher incidence of comorbidities and polypharmacy issues, but also because of biological changes that make older people more sensitive to opioids and their side effects.

The good news is that there is a tremendous amount of information about and support for effective cancer pain treatment. The World Health Organization (WHO), national professional organizations and governmental agencies of the United States have all acknowledged the importance of pain management as part of routine cancer care. Myths about opioid addiction are being dispelled, and specific guidance in the legitimate use of opioids is alleviating past fears of legal sanction.

An excellent example of these guidelines is the “Model Policy for the Use of Controlled Substances for the Treatment of Pain” adopted by the Federation of State Medical Boards in May, 2004. A copy of the model is included as Appendix B. Another valuable source for guidance, “Promoting Pain Relief and Preventing Abuse of Pain Medications: A Critical Balancing Act”, has been published jointly by health organizations and the Drug Enforcement Agency and is included as Appendix D.

Every health care provider involved in the care of cancer patients is urged to get updated information and guidelines for the competent and legal use of opioids for cancer pain relief. They are also encouraged to educate themselves on nonpharmacologic therapies that can be used in conjunction with analgesics to provide optimal pain relief and functional restoration of cancer patients.

CANCER PAIN OVERVIEW

Cancer pain includes pain caused by the disease itself and/or painful diagnostic procedures or treatments.

Nociceptive pain is the most prevalent type of pain associated with cancer. It is caused by normal activation of neural pathways in response to pain-producing stimuli. Nociceptive pain results from tissue distention or infiltration caused by a tumor, nerve compression, and/or resulting inflammation due to infection, necrosis or obstruction. Bone pain syndromes are the most common nociceptive pain syndromes. Neoplastic invasion of bone, joint, muscle, or connective tissue can cause extreme pain. Back pain is highly common among cancer patients. Nociceptive pain syndromes generally respond well to opioids.

Neuropathic pain is considered a type of chronic non-malignant pain involving disease of the central and peripheral nervous systems. Neuropathic pain may occur as a result of tumor infiltration or compression of nerves. Remote effects of malignancy on peripheral nerves can also cause neuropathic pain. Neuropathic pain may persist in the absence of ongoing tissue damage. The pain is typically characterized by aching, tingling, stabbing, electric shock-like or burning sensations. Neuropathic pain syndromes generally respond less well to opioids than nociceptive pain syndromes, and may require use of adjuvant drugs such as antiepileptic medications, anticonvulsants and antidepressants.

Antineoplastic therapies, such as chemotherapy and radiation therapy, can cause chronic pain syndromes as well. Nociceptive pain related to these therapies is rare. Most post-treatment pain syndromes are neuropathic, and reflect nerve injury. Pain is slowly progressive, and less prominent than pain caused by neoplastic nerve injury.

Chemotherapy can cause numerous side effects, depending on the medication being used. Some of the more common side effects that cause pain include mouth sores, peripheral neuropathy (numb and sometimes painful sensations in the feet, legs, fingers hands and arms), constipation, diarrhea, vomiting, and abdominal cramps. Some people also experience bone and joint pain from chemotherapy medications and from the medications used to offset the impact of the chemotherapy on blood counts and on the risk of infection.

Procedure related pain is often the result of surgery, biopsies and/or bone marrow aspirations. Children with cancer perceive the latter as extremely painful.

Although cancer pain cannot always be relieved completely, there are many therapies – both pharmacologic and non-pharmacologic – that can vastly reduce a patient’s physical, emotional and cognitive suffering.

CANCER PAIN ASSESSMENT

Pain assessment is a critical first step in developing a sound treatment strategy for cancer pain. In order to treat pain adequately, it first must be measured.

While a detailed medical history, physical exam and review of laboratory and imaging studies help clarify the relationship between pain and the disease, they do not, by themselves, establish a definitive conclusion about where it hurts, how much it hurts, and how the “hurt” is affecting the patient’s life.

Each patient’s perception of pain depends on a complex interplay of physical, emotional and cognitive components. There are no objective measures. A patient’s self-report of pain, thus, is considered the “gold standard” for optimum pain assessment. A comprehensive pain assessment should collect the following information from the patient:

• A general physical health description
• A detailed description of the pain (When did the pain start? How long does it last? Is the pain worse during a certain time of day? Where do you feel the pain? What is the intensity of the pain? Does the pain travel, and if so, where does it go? What factors make the pain worse? What factors make it better?)
• How pain affects:
  • Physical functioning (walking, bathing, dressing, climbing stairs, lifting objects, exercise, etc.)
  • Ability to work or do other daily activities, like household chores, paying bills, etc.
  • Ability/desire to participate in social/leisure activities
  • Feelings of energy and vitality
• Mental health status (Is he/she depressed? Anxious? Unable to sleep?)
• Beliefs and attitudes relating to pain and various pain treatment modalities
• History of past failures or successes and/or adverse side effects experienced with different pain treatment modalities, including analgesics and current/past use of “natural remedies,” “home remedies” and “over-the-counter” drugs

There are a variety of pain assessment tools that can be used to help gather the above information in a consistent manner, and which additionally allow for systematic measurement of pain parameters over time.

Pain scales measure the degree of pain. The best type of pain scale to use (numeric, verbal, pictorial, etc.) will depend on the age, verbal ability, literacy and cognitive functioning of the patient. For very young children, pictorial scales, such as those that use facial expressions or color intensities, are recommended. Children ages 8 and above can generally quantify their pain using a verbal analog scale.

For the elderly, the American Geriatrics Society recommends the numeric scale (see fig. 2). Pictorial scales are often used for cognitively impaired patients, or patients with limited education.

Several pain assessment tools (body diagram, visual analog and numeric scale) are included as Appendixes E-G.

Figure 2. Numeric Pain Intensity Scale

Health-related quality of life assessments, such as the SF-36 Questionnaire®³⁰ and the McGill Quality of Life Questionnaire,³¹ are valuable tools for assessing the extent of a patient’s functional impairment as well as his/her emotional responses to that impairment. In developing a pain treatment program, this information can be used to establish realistic goals for improvement, and encourages patients to participate in decision-making and be their own advocate in effecting change.

For elderly cancer patients, the Vulnerable Elders Survey (VES-13)³² is a simple function-based tool for screening community-dwelling populations. Its purpose is to identify older persons at risk for health deterioration. The VES considers age, self-rated health, and limitations in physical function, and functional disabilities. A short form Mental Status version of the SF-36 Questionnaire can be used to assess whether the patient is cognitively impaired and requires family members or a caregiver to assist in the pain assessment process. In cases of cognitive impairment, much can be learned by studying common pain behaviors such as facial expressions, verbalizations/vocalizations, body movements, changes in interpersonal interactions, changes in activity patterns or routines and mental status changes. URL addresses for the SF-36, McGill and VES assessment tools are in Appendix P.

Depression is a prevalent and serious comorbidity associated with cancer. Fortunately, it is reversible, and can be treated using a number of different modalities, including psychiatric/psychological counseling, support groups, and antidepressants. Multiple, practical questionnaires are available to help clinicians identify and diagnose patients with major depression. A Geriatric Depression Scale (GDS) is recommended for elderly patients, and a copy of a GDS is included as Appendix H. As appropriate, clinicians should refer patients to mental health care professionals for diagnostic confirmation and treatment.

TREATING CANCER PAIN

At the end of the movie Terms of Endearment,³³ Shirley MacLaine (Aurora) is at the hospital where her daughter is dying of cancer. Aurora rushes from her daughter’s room to the nursing station. She is obviously very agitated. Aurora points at her watch and says to the nurse at the desk, “It is after 10. Please give my daughter her pain shot.” The nurse responds calmly “I was going to in just a few minutes.” Hysterical, Aurora shrieks, “It’s after 10! It’s time! My daughter’s in pain! I don’t understand why she has to be in this pain! Give her a shot! A shot!”

Knowing that a loved one is in agonizing and unnecessary pain is disturbing, to say the least. The scene described above has probably been played out in hospitals or nursing homes countless times. When family members witness a loved one in terrible pain, feelings of helplessness, desperation and anger potentially can lead them to take legal action. This was clearly seen in the case of Bergman vs. Chin, in which a terminally ill cancer patient suffered excruciating pain in his final days.³⁴

Good pain control requires administering pain medications on a specific schedule or under the direct control of the patient with a specific pain-dispensing machine, not just when pain develops. The analgesic dose should effectively prevent recurrence of pain prior to the next dose. The “as needed” dosing schedule is no longer viewed as an effective pain management strategy.

The majority of cancer patients with moderate to severe pain can be successfully and safely treated with opioids. Some patients with mild pain can be treated effectively with non-opioid drugs, and these should always be considered prior to initiating opioid therapy.

A key principle in opioid therapy is individualization of the dose. Not all patients react the same way to opioids, and tolerance for side effects varies. The goal with each patient is to find an acceptable balance between pain relief and side effects. In situations where pain is being poorly controlled, the dose should be increased gradually, and side effects monitored carefully. Maximal dosage is limited by unpalatable side effects. There is no one correct or maximal dose. In some cases, it may be necessary to rotate opioid drugs in order to find optimum pain relief with minimum side effects.

Opioid Side Effects
Unpleasant (and unmanaged) side effects to analgesics can cause a patient to discontinue use of pain medication. This puts the patient at risk of unnecessary pain and associated negative health consequences. The most common opioid side effects include constipation, nausea, somnolence and cognitive impairment. It is extremely important to educate patients about possible side effects and provide solutions for minimizing their effect on the treatment goal.

The first-line approach in dealing with side effects is to switch to another opioid drug. Are the side effects resolved or mitigated? Another strategy is to try the use of another analgesic (e.g., addition of an NSAID) or nonpharmacologic treatment (e.g. neural blockade) in combination with a reduced dose of the current opioid.

There are effective strategies for reducing the discomfort of side effects when they do occur. Constipation can be addressed through diet (increase water and fiber intake) and/or laxatives. Nausea can be mitigated through hydration, progressive alimentation, good mouth care, elimination of contributory factors, and/or by adjusting the medication dosage. Pharmacological therapies are also available to reduce nausea and vomiting.

Patients with somnolence or cognitive impairment should be educated and reassured about these side effects. In most cases, these side effects abate after a few days following initiation of treatment. When these conditions persist, and if analgesia is satisfactory, a reduction in opioid dose can be considered. In some cases, psycho-stimulants have been used to reduce undesired levels of drowsiness caused by opioids.

Breakthrough Pain
Treatment of acute breakthrough pain is a common problem with cancer patients. Breakthrough pain affects about one-half to two-thirds of patients with chronic cancer pain.³⁵ Breakthrough pain is a phenomenon in which a patient experiences severe, intermittent episodes or “flares” of pain that the regularly scheduled dose of pain medication does not control.

The duration and frequency of breakthrough pain varies from person to person. It typically comes on quickly, and may last anywhere from seconds to minutes to hours. One study found that the average breakthrough period was 30 minutes.³⁶ Causes of breakthrough pain may be linked to specific physical activities, such as walking, sitting and standing and even coughing. In other cases, the triggering causes are not obvious. Most patients with breakthrough pain suffer several events per day.

In treating breakthrough pain, clinicians should first look at the timing of breakthrough pain episodes. Can they be correlated to the end of a baseline pain medication period? Does the dose of the fixed-scheduled medication need to be adjusted? Other key considerations include:

• Ease of administration
• Speed of pain relief
• Time for the drug to be secreted from the body

The majority of medications used for breakthrough pain are short acting opioids, also referred to as rescue medication. Most patients prefer oral medications. Patients who have difficulty swallowing or have nausea or other gastrointestinal problems can take pain medications by injection, sublingually, rectally or transmucosally. Physicians prescribing opioids for breakthrough pain should consult with pain medication manufacturers and professional medical organizations for guidelines on titrating breakthrough analgesic doses independently from baseline analgesic doses. As with long-acting opioids, rescue medication may also cause unpleasant side effects. Physicians should educate patients on possible side effects and have a plan in place to manage them to the extent possible.

In developing a strategy for relieving breakthrough pain, clinicians should consider using other modalities as well. Cognitive therapies such as relaxation training, hypnosis, guided imagery and distraction may provide added pain relief for some patients.

Guidelines for Opioid Use
The World Health Organization’s Analgesic Step-Ladder³⁷ approach provides excellent guidelines for the use of opioids in managing cancer pain:

• Complete a thorough patient assessment that will allow you to identify the pain syndrome(s), the functional status of the patient (effect of pain on patient’s quality of life), comorbidities, psychological disturbances/disorders, and possible history of substance abuse.
• Select analgesic therapies appropriate for the pain syndrome(s); given all assessment information, identify other non-pharmacologic strategies that would benefit the patient. As needed, refer the patient to specialists for optimal pain management outcomes.
• In selecting opioids, consider the patient’s age and medical condition, previous analgesics used (and success rates), pharmacologic issues, side effects or toxicities, drug-drug interactions, and differences in preparations/formulations, cost and availability.
• Use the least invasive route (by mouth, if possible).
• Start with a low dose and increase until analgesic efficacy is achieved.
• Use around-the-clock dosing schedule to avoid pain “troughs.”
• Individualize the treatment plan to the patient.
• Plan for and provide “rescue medication” for breakthrough pain.
• Consider disease progression when adjusting doses.
• If treatment fails to relieve pain, or if side effects are unpalatable, consider a trial of another opioid.
• Consider other interventions (nerve blocks, surgical procedures or psychological therapies) when patients do not respond satisfactorily to opioid therapy.

Opioid Use with Children and the Elderly
Although it was formerly thought that children become easily addicted to narcotics, the truth is that less than 1% of children treated with opioids develop addiction. Opioids are no more dangerous for children than they are for adults when appropriately administered.³⁸ Another obstacle to opioid use with children stems from fears about respiratory depression. While this is a concern for any patient, regardless of age, clinical studies show that it rarely occurs in children.³⁹

Parents of a child with cancer are likely to have many questions about their child’s pain. What is causing it? How will it be treated? Is addiction possible? What pain will side effects cause? And, What can they do to assist with the pain management program? Appendix I is a copy of “Four Pain Commandments for Parents.” It is marked for easy removal and reproduction. A copy of the Commandments should be given to all parents and guardians to help them provide the correct information, and ask the questions that will provide the information they want from their physician. Other educational materials on child cancer pain are listed in the Resources section.

In treating the elderly with opioids, it is critical to keep biological changes associated with aging in mind. As people grow older, the basal metabolic rate and renal system slow down and become less efficient. Drugs are retained in the system longer. This can greatly increase the toxicity of drugs with a long half-life. Accordingly, opioids that do not require metabolic activation are generally recommended. Dose escalation should be extremely slow to allow for careful measurement of adverse side effects, including respiratory depression. Additionally, because elderly patients typically take a variety of different medications, clinicians should be aware of potential interactions between non-analgesic medications and analgesics.

Nonpharmacologic Therapies
Used in conjunction with appropriate analgesics, nonpharmacologic therapies (massage, biofeedback, cognitive-behavioral therapy, support groups, relaxation techniques, guided imagery, psychological counseling, etc.) often can facilitate more successful outcomes than a treatment plan consisting strictly of pain medication. The cognitive and emotional components of a patient’s pain (and the family’s experience of that patient’s pain) deserve as much attention as the physical pain.

Pain assessment information, including pain from co-existing comorbidities, should be used to steer decision-making in selecting appropriate modalities. Additionally, age, cognitive functioning, language barriers, and cultural and spiritual beliefs should be considered. For example, non-pharmacologic approaches for a young child with cancer might include education, parental support, cognitive behavioral therapy, and distraction techniques. For an elderly person, home remedies, massage, social gatherings, prayer and music therapy might be good choices for alternative pain relief. A young adult with cancer may benefit most from counseling and support groups.

The key is to understand each patient’s specific situation, their likes and dislikes, their beliefs and attitudes about pain, and what they are willing to do to relieve their pain.

Patient involvement is very important in managing cancer pain. Included as Appendix J is a copy of a National Cancer Institute “Pain Control Record”⁴⁰ in which patients track the intensity of their pain, the effects of medication, and any other pertinent information. This record is a useful tool for the physician, and the patient should be instructed to bring a current pain record to each visit.

SUMMARY

The tragedy of cancer pain management is that despite the available technology to relieve pain, pain relief continues to elude many patients. This is not always the fault of medical professionals. Patients often are responsible for continued suffering when they fail to report pain or fail to comply with pain medicine protocols. Whatever the reason, the onus for effectively assessing and treating cancer pain falls squarely on the shoulders of health care providers. Given heightened priorities for relieving pain, education on and adherence to new pain management guidelines are important. So, too, is adoption of a philosophy that defines pain not just as the physical damage of tissue or nerves, but as a human experience of diminished life quality.

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