A model for the treatment of cancer pain

Ib/. 1 No. 4 Fall 1986

Journal of Pain and Symptom Management

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Special Article

A Model For the Treatment of Cancer Pain Charles S. Cleeland l, Armando Rotondi2, Theresa Brechner 3, Allan Levin4, Neil MacDonald 5, Russell Portenoy6, Henry Schuttal, Mary McEniry1

Departments of tNeurology and 2Industrial Engincerin~ University of Wisconsin-Madison; 3Department of Anesthesiology, University of California-Los Angeles; 4Department of Neurosurgery, University of Wisconsin-Madison; 5Cross Cancer Center, Edmonton, Alberta; 6Department of Neurology, Albert Einstein College of Medicine; Bronx, New Ibrk

Abstract Previous suggested protocols for the management of cancer pain have focused solely on the use of systemic analgesics. Studies of other modalities of pain management have reported the effectiveness of single methods of therapy (such as nerve blocks or surgical ablation), hz response to the increasing recognition that cancer pain may be difficult to ma~uzge with any single-modality therapy, we used an expert (or consensual) panel method to propose how multiple therapies (aTudgesics, mn:roablative procedures, and other non-drug therapies) might be combined in the management of patients with progressive pain. The product of this method is a decision tree suggesting the steps at which to consider various combined therapies dependent upon response to prior treatment. The decision tree is expected to have utility as an educational tool as well as a basis for generating testable hypotheses about the effectiveness of combincd therapies for future clinical research. J Pain Sympt Manag 1986;1:209-215. Key Words Cancer pain, consensual panel, pain management

There is increasing evidence that a significant proportion of cancer patients are receiving less than optimal pain relief despite prescribed analgesics. 1'2 Although it has been estimated that the vast majority of those with pain could be provided with adequate relief,3 data pooled from several studies indicate that between 60% to 80% of those with end-stage disease experience significant pain, i and that approximately one in three of those patients who have solid tumors that metastasized continue to have pain severe enough to compromise their mood and activity 4 As increasing numbers of patients live longer, a larger num-

Address reprint requests to: Charles S. Cleeland, PhD, Department of Neurolog), Pain Research Group, H6/530 Clinical Science Center, 600 Highland Ave., Madison, WI 53792

Acceptedfor publication: August 14, 1986

ber of patients have longer periods of time at risk for significant pain. Several reports have suggested that the high proportion of cancer patients with persistent pain is due to a large extent to the inadequate application of existing modalities of pain management. This deficiency, in turn, has been attributed to the inadequate preparation of medical students and physicians-in-training for the special problems of cancer pain management, the paucity of easily available information about the use of pain control modalities, and the lack of specialized resources necessary for pain management. 5 Recently there have been some important efforts to meet the need for specific information in this area. The World Health Organization has offered a protocol for the use of analgesics for cancer pain control, utilizing medications readily available in many developed countries. 6 This protocol is presented as a "ladder" of pain severity, with indications of

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when a switch from non-opioid (aspirin or acetaminophen) to orally-administered o p i o i d (codeine, then m o r p h i n e sulphate) analgesics is indicated. T h e Committee on Standards o f the American College o f Physicians has issued a position p a p e r acknowledging the need for more adequate pain treatment for the terminally ill and offering guidelines for the use o f analgesics. 7 A p a p e r has presented a summary o f guidelines for analgesic management in terminal illness, which were formulated at a conference jointl.y sponsored by the American Medical Association and the Public Health Service.8 This last report is quite detailed as to the type, dosage, and route o f analgesic appropri,ate for different clinical situations and also evaluates adverse side effects. Ahhough the r e p o r t recognizes the need for a multi-disciplinary effort for optimal management, no guidelines for treatment other than by systemic analgesics are offered. Finally, a recent monograph by the H e a h h Ministry of the Canadian Government addresses drug management o f cancer pain in detail, and also includes mate. rial on pain assessment and methods o f pain management by means o t h e r than the use o f system!c analgesics. ~ T h e present effort was based on the premise that optimal management for pain due to cancer requires the integration o f a variety of pain m a n a g e m e n t t e c h n i q u e s . A l t h o u g h it is assumed that systemic analgesics will be the major pain control tools to be used, there is increasing recognition of the contribution o f other modalities o f therapy, such as the reduction o f tumor mass, neuroablative procedures, neurostimulation techniques, temporary nerve blocks, physical therapy, and nursing and behavioral/psychological interventions) ~ T h e dearth o f controlled o u t c o m e studies, especially those employing muhiple therapeutic modalities, on these techniques was also recognized. We perceived a need for a model that would suggest how diverse pain therapies might be combined for maximal pain control. This model could serve both as an instructional tool and as a basis for formulating testable hypotheses about the effectiveness o f combined treatments. Because of the lack o f o u t c o m e research, the model by necessity n e e d e d to be generated as a consensual product o f persons with acknowledged expertise in cancer pain management. It was recognized that the model might poten-

Journal tf Pain and Symptom Management

tially attract dissenting views, but that this discussion would be extremely fruitful. We selected a m e t h o d for developing a consensus o f expert recommendations which is based on the Integrativ e G r o u p Process, develo p e d by Gustafson, Fryback and Rose n at the University o f Wisconsin Center for H e a h h System Research and Analysis. This method was chosen over other methods to develop consensus with a group because it was designed to address complex problems in heahh care, such as assessment o f burn severity~2 and determination o f trauma severityJ 3

Method Panel Selection Both the medical specialties to be represented in the panel as well as the individual r e p r e s e n t a t i v e s o f these specialties were selected by a nomination process conducted by telephone inter~,iew with persons who had achieved recognition as authorities in cancer pain management. T h e final panel composition included an oncologist, an anesthesiologist, a neurologist, and a neurosurgeon. T h e panel was chaired by a neurologist from o u r own institution who is familiar with the panel process, and also with the etiology o f cancer pain. The panelists a p p e a r as co-authors o f this report. Telephone hllerviews hnmediately prior to convening the panel, each o f the panel members was interviewed by telephone. Information from the interviews was used to determine the factors that each m e m b e r felt were important to their selection " o f p r o p e r treatment. To ensure that this information reflected the clinical approach o f the panelist, each was placed in a practical setting by acting as consultant to the interviewer, who played the role o f a physician needing advice on a hypothetical patient experiencing pain due to cancer. T h e panelist was allowed to think about the problem and then was asked for the information about the patient that was needed to determine appropriate therapy For each o f the panel's requests the inter~,iewer determined: (a) the possible values that the information could assume (b) the treatment recommendations suggested by the various values, and (c) additional information that the values indicate

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A Model for 7i-eatment of Cancer Pain

might be needed. From these data, pooled from all panelists, a preliminary model o f cancer pain management was created.

Consensual Modeling Procedures Session One T h e first meeting day which lasted approximately eight hours, began with an introduction o f the panel members and a brief statement about each person's area o f specialization. T h e model building p r o c e d u r e was initiated by presenting the preliminary model created from the telephone interviews to the panel. T h e strengths and weaknesses o f the preliminary model were noted. A consensus model was then built that avoided tile weaknesses o f this model, and incorporated its strengths. T h e day's session was concluded by adjusting the model in two ways: first, by examining the model's treatm e n t r e c o m m e n d a t i o n s for realistic b u t unusual patient situations that might arise, and, second, by c o m p a r i n g the model's treatment o f hypothetical "patients" to those agreed u p o n by the panel based on their clinical experience.

Session Two T h e final procedure o f the meeting process was to compare treatment recommendations for patient case studies (taken from o u r own files) with the panel's group recommendations. If the model did not closely imitate the panel, it was adjusted each time.

Follow-up "In the three months following the panel meetings we began an iterative process to check and verify the model. This process provided the members with an o p p o r t u n i t y to reflect u p o n the model in the light o f their clinical practices, subsequent to the panel meeting.

The Model T h e product o f the panel process was a flow diagram o f cancer pain management, which is presented on pp. 212-213. Annotation o f the model, explaining the branching points o f the diagram, is presented on p. 214. The decision tree begins with the r e p o r t o f pain in a patient with active disease. At each branching point,

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there is the possibility that pain will be adequately managed. T h e panel emphasized, however, the need for frequent reassessment o f t~e patient in order to detect changes in pain. T h e panel developed several points that could be considered general principles o f good pain management. Thes_e principles included: 9 T h e need to consider the application o f several modes of pain therapy simultaneously, not sequentiall); 9 Symptoms associated with severe pain, including m o o d and sleep disturbance, must be addressed in c o m p r e h e n s i v e pain management, 9 Adequate analgesics should be provided to the patient who has active disease without regard to prognosis or to the potential outcome o f the patient's anti-tumor therapies, 9 T h e patient's r e p o r t o f pain severity should be the primary basis o f analgesic choice and dose, 9 If no a d e q u a t e pain relief is obtained, patients should be advanced to more potent analgesics rapidl); 9 Analgesics should be administered on an around-the-clock basis, 9 Tile continuous evaluation of the possible role o f anti-tumor therapy for pain relief must not be abandoned, 9 Negative side effects o f narcotics, especially constipation, should be anticipated and preventative measures taken before, not after, they occur,

9 T h e r e is an i m p o r t a n t role for switching narcotics because o f incomplete analgesic crosstolerance, and, 9 T h e r e is a definite place for neuroinvasive procedures, including destruction of nerve pathways, in the m a n a g e m e n t of pain due to advanced cancer.

Discussion Tile final model satisfies tile objective o f presenting a format for the use o f combined therapies for managing cancer pain. Its iterative character forces one to consider the frequent adjustment o f therapeutic strategies that are necessary as pain becomes more severe. While clinical research s u p p o r t for many o f the steps in the model can be offered, the major weakness o f this model (or any other o f this type) i s that many of its assumptions need to be tested exnpiricall)z T h e difficulties of testing combined therapies remains, but the model can be

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Journal of Pain and Symptom Management

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Journal of Pain and Symptom Management

Footnotes for Pain Treatment Flow Chart 1. Treat patient's pain according to indications. Monitor for recurrence of cancer. 2. Evaluate patient for anti-tumor therap), or changes in current anti-tmnor therap): 3. The patients' treatment is selected to match their level of pain, not the etiology of the disease. 4. First try a nonsteroidal anti-inflammatory drug. Most of these drugs have ceiling effects indicating that increasing dosage will not provide additional analgesia after ceiling dose is reached. If customary dosages fail to provide adequate analgesia, try switching drugs or adding an opiate. 5. Start with titration of an opiatelnonsteroidal combination drug (eg, codeine/aspirin). The physician must be aware of reaching unacceptable side effects before analgesia occurs with these drugs. If pain continues at the maximum tolerable dose, switch to a potent opiate. 6. Administer a potent opiate. Titrate upward until dose has been reached for appropriate analgesic effects, or unacceptable side effects occur. For a patient who is not currently receiving opiates, one may try an opiate/nonsteroidal combination drug (eg, codeine/aspirin) for a brief period--typically this will only be for one or two days~to see if this will provide adequate pain control. 7. This means that the patient does not have any associated symptoms such as sleep disturbance, nausea, depression, sedation effects, or constipation.

considered as a set o f hypotheses, based on c o m b i n e d clinical experience, which are o p e n to empirical test. Validation o f the model might be accomplished in several ways: At a preliminary level, the severity o f pain o f patients now managed as the model specifies could be compared with the pain o f those patients whose pain managem e n t differs from the. model in significant respects. I f this comparison were to be made, it would be necessary to control for several factors, such as site and stage o f disease, and metastatic sites, which are known to influence tile severity o f cancer pain. At a second level, prospective studies could be designed (again, controlling for disease-related variables) where elements o f the combined therapies suggested by the model are systematically evaluated.

8. The treatment of sedation with stimulants is still controversial and remains a subject for clinical research. 9. Other nonsteroidal anti-inflammatory drugs may also be used; however, there is no evidence of benefit from combining them. 10. This includes TENS, acupuncture, counter. irritation, etc. 11. If new pain occurs, return to "assess patient's pain lever' in model, where patient's pain severity is assessed. 12. Clinical evidence suggests that the new drug should be started at one-half to two-thirds the equianalgesic dose due to incomplete cross-tolerance between opiate drugs. This starting dose can then be titrated upward if necessary. 13. Some of the procedures listed here may only be available at some medical centers. 14. Chemical or surgical. 15. Celiac plexis blocks have been found to be very effective in treating pain due to pancreatic cancer. It may be appropriate to use this procedure during the early stages of pain management in these cases. 16. Return in model to patient's pain level assessment after a neuroinvasive procedure has been used.

The model may also fidfill a function as a teaching tool. Its major advantage is that it illustrates the complexity o f pain management in a m a n n e r that is comprehensive and relatively easy to understand. Its graphic presentation underscores tile panel's emphasis on simuhaneously applied therapies.Just as the panel did in its construction, the reader can follow specific cases along the path o f the model in o r d e r to formulate a therapeutic strategy to be considered. The model can be adjusted as new data on therapeutic effectiveness require. As part o f the process o f model development, the panel members became aware o f several questions that the model does not /~dequately address. First, it became clear that the problem o f persistent post-therapeutic pain was beyond the scope o f this initial effort. Seo

lbl. I No. 4 Fall 1986

A Model for 7)vatment of Cancer Pain

ond, while the panel stressed the i m p o r t a n c e o f the patients' r e p o r t o f pain as the m a j o r determ i n a n t of a p p r o p r i a t e pain therapy and its effectiveness, panel m e m b e r s noted that the clinical assessment of p a i n severity is often difficult. Although it was recognized that a standard format o f pain assessment was essential, the panel was not able to offer an agreed u p o n r e c o m m e n d a t i o n o f how this is to be d o n e . Third, although all panel m e m b e r s agreed that behavioral/psychological interxentions should be an integral p a r t o f comprehensive pain m a n a g e m e n t , it was felt that r e c o m m e n d a t i o n s for specific therapies o f this type should c o m e from a group with greater expertise in this area. Finally, although not specified in the model, the panel m e m b e r s u n d e r l i n e d the i m p o r t a n c e o f allowing the patients' wishes to d e t e r m i n e the balance between level o f pain relief and the potentially o b t u n d i n g effects o f high levels o f analgesic medication.

Acknowledgment T h i s r e s e a r c h was s u p p o r t e d by g r a n t CA26582-06, awarded by the National C a n c e r Institute.

References

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9. Health and Welfare, Canada. Cancer Pain. Ref #H42-2/5, 1984. 10. Foley KM. The treatment of cancer pain. N Engl J Med 1985; 313:84-85. 11. Gustafson DH, Fryback, DG, Rose G. Severity I n d e x M e t h o d o l o g y D e v e l o p m e n t Research Project. Report #5-R18-HS02621. The National Center for Health Services Research, 1981;June. 12. Gustafson DA, Hollowa}, D. A decision theoretical approach to measuring the severity of burns. Health Services Research Journal 1975; Spring: 001-007. 13. Baker S, O'Neill R, Huddon W, Lang W. The injury severity score: A method for describing patients with multiple injuries and evaluating emergency care.J Trauma 1984; 14:3.