The Pharmacologic Management of Cancer Pain

The Pharmacologic Management of Cancer Pain

Dr. Cherny's article on the management of cancer pain is a comprehensive review that should prove to be a helpful resource. As physicians in a palliative care and oncology program, we discuss how we utilize these principles and what we see put into practice by others. Cherny and Catane have already documented that the great majority of oncologists do a substantial amount of palliative care, whether they call it that or not, and that most oncologists would be willing to work with palliative care or symptom management specialists.[1] Knowledge is only one part of the solution, and must be paired with better practice by health-care professionals and help from our patients. Articles like this will only help if oncologists pay attention. Current State of Pain Control
All the available data suggest that pain control is still not optimal, and that it can be improved. In a trial done at community oncology practices in 1997, DuPen and colleagues randomized patients to two treatment arms: group 1 received standard care; group 2 was interviewed by a nurse practitioner to ascertain pain scores, then the pain was managed by the nurse/ doctor team according to the Agency for Health Care Policy and Research (now Agency for Healthcare Research and Quality) guidelines[2] made into a proprietary guideline. The standard group made no improvement, even when the practitioners knew the study was ongoing in their office. The intervention group had a significant reduction in pain that was sustained, as shown in Figure 1.[3] Miaskowski and colleagues documented that only 29.2% of their chronic cancer pain patients were prescribed an analgesic regimen that included both around-the-clock dosing for long-acting opioids and "prn" dosing for short-acting opioids, even though guidelines have suggested this for years.[4] Data from the Cancer Pain Trial showed that the control group, now comanaged by the oncologist and a pain specialist instead of the oncologist alone, had a 39% reduction in pain scores![5] The fact that the control group could have a 39% reduction in pain scores and a 17% reduction in drug toxicity shows that we still have a long way to go. We participated in a recent University Hospital Consortium (UHC) study, with an audit of 50 patients, that showed that only about 70% of patients had pain relief by 48 hours in the hospital, and only about 60% who got opioids also got a bowel regimen to prevent constipation. Again, some health systems did much better than others (unpublished data). Opioid Side Effects
Dr. Cherny's review of opioid side effects was superb. Some side effects can be anticipated and prophylaxis initiated, while others cannot. Data from the UHC study appear to show that even simple procedures like prescribing a bowel regimen alongside narcotics are done only half the time. Actual side effects or the perceived possibility of side effects often hinders effective dosing of narcotics. For example, many patients are often underdosed for fear of respiratory depression. Patients may also underreport their pain for fear of becoming addicted or taking too much medication. When narcotics are titrated upward based on usage, the risk of respiratory depression or sedation is lessened. In such ill and complicated patients, a change in their condition should not automatically be ascribed to the narcotic. Often an acute change in a patient on a stable narcotic dose is not due to the narcotic. Also, the oncologist needs to consider the interaction of other medications- particularly benzodiazepines- which can increase the risk of altered mental status and respiratory depression, especially in combination with opioids. Dr. Cherny points out that improvement in a patient's condition after administration of naloxone may not be proof that the patient was oversedated by opioid. He notes that this improvement may be due to "intercurrent cardiac or pulmonary process." We felt that this interesting point deserved further discussion by the author, to give us clues in differentiating the processes. What is important is that reassessment of the whole patient is continuous. In addition, when interventions or adjunctive agents lead to a reduction in pain, narcotic requirements may decrease. This may lead to more sedation and respiratory depression if the narcotic dose is not decreased accordingly. Although pain is often undertreated due to the fear of respiratory depression and oversedation, when opioids are used properly these problems are rare. However, it is important to know the indications for opioid reversal and how to administer naloxone correctly. If a patient has a decreased respiratory rate but is easily arousable, naloxone need not be administered. The narcotic dose may be decreased or stopped until respiration or mental status improves. When the respiratory rate is below 6, naloxone should be administered by diluting the solution 1:10 and administering 1 mL at a time. This will allow reversal of respiratory depression, while decreasing the likelihood of the patient experiencing a traumatic loss of pain control. In addition, naloxone's halflife (30 to 40 minutes) is shorter that most narcotics and it may need to be readministered, or even an IV infusion begun depending on the situation. Patients should be monitored closely after receiving naloxone. Pharmacology of Opioids
Dr. Cherny's section dealing with opioid pharmacology was comprehensive but readable. In addition, one should consider underlying disease states for choice of the appropriate narcotic. For example, fentanyl and hydromorphone might be more appropriate for patients with renal or hepatic failure, respectively, to decrease the accumulation of metabolites. As a patient's condition changes or declines, alternative routes of administration may need to be used. It is important to be comfortable prescribing various routes of administration of opioids to accommodate the patient with changing clinical issues such as loss of IV access or vomiting. In general, we avoid intramuscular pain medications. Also, note that subcutaneous access is an easy, effective, and yet often underutilized route of administration. Adjunctive Agents
The review of adjunctive agents for neuropathic pain reinforces the statement that pain management is a multidisciplinary approach and that anesthesiologists and interventional radiologists should be involved. We have also found lidocaine patches to be effective for incisional pain, postmastectomy pain, and lumbar pain secondary to lumbar disk disease, but there are no published clinical data yet to support this practice for cancer-specific pain. In our practice, we have applied many of the premises of relief of malignant pain to nonmalignant syndromes such as reflex sympathetic dystrophy, herpes zoster, neuropathy, severe osteoarthritis, or compression fractures. The evidence available to support implantable intraspinal drug delivery devices (IDDS) has improved recently. The Cancer Pain Trial was an international, multicenter, allocationblinded randomized controlled trial of IDDS plus comprehensive medical management (CMM) vs CMM alone in 202 cancer patients with an average pain visual analog scale (VAS) score of 7.5 despite a median opioid dose of over 200 mg of morphine or equivalent. The CMM clearly reduced pain VAS scores, by opioid titration and addition of other analgesics, as shown in Figure 1. The IDDS + CMM patients achieved a 52% reduction in pain scores, a 50% reduction in drug side effects, and lived longer. These reductions in pain scores and side effects persisted for the length of the trial or until death,[6] and IDDS helped even the most refractory patients- those refractory to CMM.[7] These large randomized trial results, when added to the multiple Level II single-institution studies, provide compelling evidence for the effectiveness of IDDS.[8] Commonly used indications for IDDS include uncontrolled pain despite 200 mg of morphine or equivalent or uncontrolled side effects from opioids, and the absence of contraindications, such as obstructed spinal fluid flow or short lifespan. Patient Self-Management
The other exciting area that will help oncology patients is better selfmanagement. While space does not permit a review of the accumulating evidence, one study published in the Journal of Clinical Oncology stands out. Miaskowski and colleagues showed that a relatively simple and affordable psychoeducational intervention- coaching, phone calls, and home visits-improved compliance with appropriate prescribing and, more importantly, decreased usual pain scores by over 30% compared to usual care.[9] Conclusion
In conclusion, Nathan Cherny provides us with a concise, thoughtful summary of the current state of cancer pain management. His paper should prove to be a useful resource for any practitioner caring for patients with pain. If information were the problem, papers such as this from recognized experts would have fixed nontreatment of pain. Just as importantly, we as oncologists need to recognize that we are not doing an optimal job in controlling symptoms, and that we can do better. To properly do palliative care, which is the bulk of oncology work, we need help from other members of the health-care team, including nurses, advanced practice nurses, and patients.


Dr. Smith has received grant support from the Robert Wood Johnson foundation; he has received unrestricted grant support and lecture honoraria from Medtronic, Inc.


1. Cherny NI, Catane R, European Society of Medical Oncology Taskforce on Palliative and Supportive Care: Attitudes of medical oncologists toward palliative care for patients with advanced and incurable cancer: Report on a survey by the European Society of Medical Oncology Taskforce on Palliative and Supportive Care. Cancer 98(11): 2502-2510, 2003.
2. Clinical Practice Guideline Number 9: Management of Cancer Pain, AHCPR publication 94-0592. Rockville, Md; US Dept of Health and Human Services, Agency for Health Care Policy and Research; 1994
3. DuPen S, DuPen A, Polossar N, et al: Implementing guidelines for cancer pain management: Results of a randomized controlled clinical trial. J Clin Oncol 17:361-370, 1999.
4. Miaskowski C, Dodd MJ, West C, et al: Lack of adherence with the analgesic regimen: A significant barrier to effective cancer pain management. J Clin Oncol 19(23):4275-4279, 2001.
5. Smith TJ, Staats PS, Deer T, et al: Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol 20:4040-4049, 2002.
6. Smith TJ, Coyne PJ, Staats PS, et al: Implantable drug delivery systems (IDDS) provide sustained pain control, less drug toxicity, and better survival compared to comprehensive medical management (CMM) (abstract 2967). Proc Am Soc Clin Oncol 22:738, 2003.
7. Coyne P, Smith T, for the Implantable Drug Delivery System Group: Implantable drug delivery systems (IDDS) after failure of comprehensive medical management (CMM) can palliate symptoms in the most refractory cancer pain patients (manuscript under review).
8. Smith TJ, Coyne P, Staats P: Implantable drug delivery systems: What is the evidence? Support Cancer Ther 1:1-5, 2004.
9. Miaskowski C, Dodd M, West C, et al: Randomized clinical trial of the effectiveness of a self-care intervention to improve cancer pain management. J Clin Oncol 22(9):1713- 1720, 2004.
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