A New Look at Calcitonin For Metastatic Bone Pain Management
February 1, 2000 4 minutes read
A New Look at Calcitonin For Metastatic Bone Pain Management
ABSTRACT & COMMENTARY
Synopsis: Twenty-two patients with advanced cancer and bone metastases were treated in a non-randomized pain management trial of salmon calcitonin administered with morphine, both by continuous subcutaneous infusion. The results indicate that the treatment was effective, in that pain scores (by visual analogue) fell and beta endorphin levels rose in response to adding calcitonin to a stable dose of morphine. This appears to be a useful combination, although further, larger studies are warranted.
Source: Mystakidou K, et al. J Pain Symptom Manage 1999;18:323-330.
The management of bone pain from metastatic disease is often problematic and frequently requires high doses of narcotic analgesics. In this report from Areteion Hospital in Athens, Mystakidou and colleagues examine the potential role for continuous, subcutaneous infusion of salmon calcitonin (sCT) as an adjunct to morphine for patients with advanced metastatic bone disease.
The study consisted of 22 patients with bone metastases. Pain control was initially controlled by continuous infusion (sc) morphine. To be eligible for this study, initial pain control could require only low-to-moderate doses of morphine (10-20 mg/d). An additional 10 patients were initially enrolled but did not reach a pain control plateau at a morphine dose in this range, and they were treated by morphine dose escalations alone (without sCT).
Once a plateau of pain relief was reached, patients were observed for a recurrence of pain. At that time, continuous sc administration of 400 IU/d sCT was initiated while the morphine infusion was maintained at the same dose. Beta-endorphin blood levels were measured before sCT administration and 12, 24, 48 hours, and seven days after the treatment was begun. Pain scores were monitored by a visual analogue scale (1-10). A complete blood count and biochemical profile were monitored during therapy as well.
The mean pain score before the calcitonin administration was 4.43 and the score on the seventh day was 1.17. The gradual reduction in pain score was associated with an increase in beta-endorphin (increase to 147.2% of baseline by day 7). No significant side effects were observed.
Mystakidou et al suggest that sCT infusion may be a useful adjuvant analgesic when combined with relatively low doses of morphine in continuous sc administration for management of metastatic bone pain.
COMMENT by William B. Ershler, MD
Achieving satisfactory analgesia remains a goal in the management of pain from bony metastases and narcotic analgesics and radiation therapy are the standards of care. This report offers a new look at calcitonin as an adjunct to these approaches.
Endogenously, calcitonin is a thyroid hormone with complex functions that primarily include the regulation of calcium metabolism. However, calcitonins most likely have a central nervous system effect, inasmuch as there are high levels of calcitonin in the brain, particularly in the hypothalamic regions, close to those areas known to be associated with pain.1 Furthermore, circulating calcitonin levels have been shown to correlate with endorphin and adrenocorticotropic hormone (ACTH) release.2 Analgesic effects of calcitonin have been recognized and are believed to relate to these CNS effects. Increases in beta-endorphin level have been demonstrated after intrathecal, intravenous, and intranasal injections of calcitonin.3,4
Pharmacologically prepared calcitonins have varied in their analgesic properties, and it is apparent from a number of studies that the salmon variant is effective (discussed in the current manuscript). Various routes have been used, but in typically lower doses (100-200 IU) than used in this study (400 IU by continuous infusion).
The results of this study indicate that the combination of sCT with morphine, administered together by continuous subcutaneous infusion, is an effective analgesic regimen. Both subjective pain measures (by visual analogue score) and beta-endorphin serum levels would support this conclusion.
However, this was a small study, only 22 patients, and of these, there were a few (n = 3) for whom no analgesic effect of sCT could be demonstrated. A larger study is warranted. Furthermore, for patients living at home, or even for those in the hospital, continuous subcutaneous infusion might be problematic. One wonders whether preparation of sCT in a non parenteral form that would allow sustained blood levels would offer the same salutary effects.
References
1. Fischer JA, et al. Proc Natl Acad Sci USA 1981;78: 7801-7805.
2. Laurian L, et al. Horm Metab Res 1986;18:286-271.
3. Fraioli F, et al. Eur J Pharmacol 1982;78:381-382.
4. Fiore CE, et al. Int J Clin Pharmacol Res 1983;3: 257-260.
Which of the following statements about calcitonin pain treatment for patients with advanced cancer is true?
a. It is effective in combination with morphine in reducing pain.
b. It is most likely effective due to its direct effect on the osteolytic bone process.
c. It cannot be used in combination with other analgesic medications, including morphine.
d. The frequency of side effects preclude its common usage.
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