Pain Control in Patients With Cancer

Introduction

Pain is the most common symptom of patients with advanced cancer.[1-4] The importance of pain is magnified by the interaction of pain and its therapies with other common cancer symptoms such as fatigue, weakness, dyspnea, nausea, constipation, and delirium.[2,5] A patient with unrelieved pain cannot sleep well and may become fatigued. If more pain medication is taken than is needed, sedation occurs. If nausea occurs, then oral therapy is difficult. Pain medicines can add to confusion or cause constipation and nausea. Alternatively, opioids for pain can help relieve dyspnea and cough.

The fear of pain continues to be one of the greatest concerns of patients with advanced cancer and has led to such desperate acts as physician-assisted suicide.[6] This desperation is a real tragedy because we have the tools and techniques to effectively relieve cancer pain.[7-11] Cancer pain can be controlled with good comfort and function in 85% to 95% of patients with an integrated program of palliative anticancer therapies combined with an individualized regimen of systemic analgesics and coanalgesics. The appropriate use of invasive procedures can help most of the remaining patients.[12-14] In the final days of life, pain not controlled by therapies aimed at both comfort and function can be relieved by intentional sedation.[15,16] Based on current knowledge, no cancer patient needs to live or die with unrelieved pain.

Basics of Pain Control

There are three basic approaches to the control of any pain: 1) modify the source of the pain; 2) alter the central perception of pain; and 3) block the transmission of the pain to the central nervous system.[17] For example, dental pain from a severely decayed tooth may warrant an extraction or a root canal, and treatment with a regional nerve block using a local anesthetic, a fixed-combination preparation of an opioid and a nonopioid analgesic. Coanalgesic therapy for these pains consists of antibiotics and nonsteroidal anti-inflammatory drugs. Therefore, the basic approach for dental pain might be a dental procedure, a regional anesthetic block, and penicillin, ibuprofen(Drug information on ibuprofen), and hydrocodone(Drug information on hydrocodone) plus acetaminophen.

The vast majority of cancer patients can have their pain relieved through direct and indirect modification of the source of their pain combined with pharmacologic and nonpharmacologic alteration of their perception of pain.[7-9,18,19] The most common source of cancer pain is the cancer itself. Alternatively, cancer treatment can produce both acute pain and chronic pain,

such as mucositis and postsurgical neuropathy, that require their own specific coanalgesic therapy. Cancer patients can also experience pain from coincidental sources such as infection or degenerative arthritis. Clinicians most commonly alter central perception of pain with opioid analgesics. Perception can also be altered with psychological and behavioral interventions. Blocking pain transmission is most suited for patients who have regional pains or who have pain that is not being controlled with acceptable side effects despite aggressive pharmacologic tailoring. The most commonly used procedural interventions include regional neurolysis and spinal administration of opioids and coanalgesics.[12-14]

Clinical Strategy

A clinical strategy for cancer pain relief consists of five sequential components: patient assessment, care plan development, care plan implementation, reassessment, and treatment modification. Patient assessment begins with determining the intensity, quality, location, and temporal pattern of each pain. Next, the patient’s cancer status, concurrent medical problems, and psychosocial status must be reviewed. It is critical to determine whether the source of the pain is progression of the cancer, residual tissue damage from the cancer and its therapy, or a coincidental problem. If the cancer is progressive, what is the likelihood that further anticancer treatment will help? What is the patient’s prognosis? Concurrent medical problems can cause pain and can interfere with analgesic therapy. For example, severe gastric ulcer disease, hypertension, or coronary artery disease can limit the utility of some of the coanalgesics. If the patient is infected or has a low platelet count, invasive procedures will have to be delayed. Assessment of psychosocial status must include the patient’s precancer psychological history as well as any current problems he or she has coping with pain or cancer.

It is the interface of these four spheres—pain, cancer, other medical problems, and psychosocial status—that guides therapy. It is critical to use this comprehensive assessment to formulate an individualized care plan for each patient. What is thought to be causing this pain? What kind of initial pharmacological therapy is preferred? What are our second- and third-line therapeutic considerations? What kind of psychosocial support does the patient need? What studies are needed to make or confirm a diagnosis of the source of the pain or the status of concurrent medical conditions? What kind of procedural interventions could help this patient and when should the anesthesiologist be consulted? A patient with deep boring abdominal pain from pancreatic cancer will often benefit from a celiac plexus block. We try to offer this block to patients before it becomes infeasible due to depression of the patient’s platelet or white blood counts from their anticancer therapy.

Ongoing Assessment

Comprehensive assessment facilitates the differential diagnosis of the source of the pain. To illustrate, a woman was recently referred for treatment of peripheral neuropathy from her paclitaxel(Drug information on paclitaxel) (Taxol) and platinum chemotherapy for ovarian cancer. She was in such severe pain that she could not get out of bed for her next appointment. When assessed, she was found to have both peripheral neuropathy and severe sciatica. Specifically, she had pain that radiated down into her buttocks, and the back of her right thigh, which is not consistent with the usual stocking-glove distribution of peripheral neuropathy. Her peripheral neuropathy was treated with a tricyclic antidepressant and low-dose opioids, and initiated a trial of dexamethasone(Drug information on dexamethasone) for her acute sciatic radiculopathy. Her pain and mobility improved dramatically and her lumbosacral MRI showed lateral spinal stenosis from degenerative disk disease. Her pain from peripheral neuropathy improved on nortriptyline(Drug information on nortriptyline), but her sciatic pain returned when the dexamethasone was lowered. She received an epidural steroid injection, which reestablished her comfort and function without the risk of systemic steroid toxicity. The net result of this interactive process of reassessment and care plan modification was a marked improvement in the woman’s quality of life.

Pharmacologic Management of Cancer Pain

Systemic pharmacologic therapy is the mainstay of cancer pain managment, but oncologists must undertand the potential of neuraxial application of pharmacologic agents or neurolytic nerve blocks. Systemic therapy must be optimized by selecting the right analgesic right dose, right route, and right interval (Table 1).[10] This analgesic is given around-the-clock to prevent chronic pain and offered as-needed to relieve breakthrough pain. Analgesic doses must be aggressively titrated and common side effects must be anticipated, prevented, and treated. Comfort and function can be further optimized through sequential opioid rotation and appropriate use of pain-specific coanalgesics.

Pharmacologic management must be individualized for each patient with the initial aim of keeping things as simple and noninvasive as possible. Patients with advanced cancer are often overwhelmed by the progression of their disease and the toxicity of their anticancer therapy. The easier they find it to gain control of their pain, the better. Since patients vary in their response to different opioid analgesics, it is important to have a working knowledge of equianalgesic tables to be able to switch from one opioid to another.[7,10,11] It is even more critical to have the time and skill to talk with patients and their families to assure them that addiction and tolerance are not real issues in the management of advanced cancer pain.[7,11]

Selecting the Right Opioid and Dose

Selection of the appropriate analgesic depends upon the patients’ pain intensity and their current analgesic therapy.[7,10,11] Pain can be measured with simple unidimensional instruments, like a numeric scale or visual analogue scale, or more comprehensive scales, like the Brief Pain Inventory.[20] By correlating pain intensity scores from the latter instrument with the impact of the pain on aspects of their quality of life, it has been shown that patients with a score of 1 to 3 can be considered to have mild pain, 4 to 6, moderate pain, and 7 to 10, severe pain.

Before selecting an analgesic to treat a patient’s severe pain, one has to know what pain medications he or she is already taking. A pain rated 6 by someone who’s not taking any analgesic might go away with a simple nonsteroidal anti-inflammatory agent. Patients with a pain of 6 out of 10 who are already taking 300 mg of controlled-release morphine(Drug information on morphine) will most likely need 450 or 600 mg of controlled-release morphine for relief.

 Most patients with advanced cancer will need World Health Organization (WHO) step three opioids: morphine, oxycodone(Drug information on oxycodone), hydromorphone(Drug information on hydromorphone), or fentanyl(Drug information on fentanyl).[7,11] These single-entity opioid analgesics are free of the dose-limiting aspects (i.e., the maximal safe dose of the nonopioid component) of WHO step two fixed-combinations of opioids plus nonopioids, such as codeine(Drug information on codeine) plus acetaminophen or hydrocodone plus ibuprofen. It is important to use step three opioids one at a time to allow for sequential trials of alternative opioids should the patient experience unacceptable side effects from the first drug.[21-24] Patients receiving controlled-release morphine should be on immediate-release morphine for breakthrough pain. Those receiving controlled-release oxycodone should have immediate-release oxycodone available for rescue doses. Meperidine (Demerol) should be avoided because of its toxic metabolite, normeperidine.[7,10] There are new reasons to learn how to use methadone(Drug information on methadone) in sequential opioid trials,[22,24] it is usually not a first drug due to its prolonged metabolism and risk of delayed accumulation.[7,10,11]

When switching from one opioid to another, and from one route of opioid administration to another, the clinician must know how to utilize an opioid equianalgesic table (Table 2).[7,10,11] These tables offer relative analgesic equivalencies to guide dose conversions. Most cancer patients will need more than one opioid and more than one route of opioid administration over the course of their disease.[7,19] The parenteral route is more potent, but not more effective, than the oral route.[7,11] When switching from the oral route to the parenteral route or vice versa, dose adjustments must be made for optimal safety and efficacy.

For most cancer pain patients, most clinicians use controlled-release morphine and immediate-release morphine,[25,26] controlled-release oxycodone and immediate-release oxycodone.[27,28] For patients who cannot swallow or be relied on to take oral medications twice a day, transdermal fentanyl (Duragesic) is an excellent alternative for control of their persistent pain.[29,30] A long-acting form of hydromorphone should be on the market sometime in the next year.[31]