Continuous subcutaneous administration of high-dose salmon calcitonin in metastasis: Pain control and beta-endorphin plasma levels

Kalle Varav, M.D.

K Mystakidou, S Befon, K Hondros, E Kouskouni, L Vlahos, Journal of Pain and Symptom Management, Vol 18, No 5, November 1999

Metastatic bony involvement is frequently a problematic source of pain for patients with advanced cancer. The armamentarium for symptom management is limited and often ineffective. Calcitonins are endogenous peptides involved in calcium regulation and bone metabolism, which have been shown to have intrinsic analgesic effects as well in both animal and human experimental studies. Data supporting this include findings of elevated beta-endorphin levels after intravenous, intrathecal, and intranasal calcitonin administration as well as discovery of the presence of calcitonin binding sites in hypothalamic regions involved with pain transmission. Specifically, salmon calcitonin (sCT) has been shown to have superior analgesic efficacy over human calcitonin in the management osteolytic bone metastasis.

The purpose of this prospective, non-randomized study was to evaluate the efficacy of continuous subcutaneous sCT administration for pain control and to determine the relationship of analgesia with beta-endorphin levels in patients with terminal cancer and metastatic bone pain.

Thirty-two patients with advanced cancer and painful bony metastasis were initially treated with continuous subcutaneous infusion of morphine. Additional medications including anti-inflammatories, antiemetics, and laxatives were also administered as necessary. Initial morphine dosages varied from 10-20mg per day. Of these initial 32 patients, 22 patients were selected for the study and received a continuous infusion of 400 IU/day of sCT along with the morphine. Selection criteria included informed consent, a reappearance of bony metastasis pain after an initial pain free interval of at least 18 days, a Karnofsky Performance status of at least 50, and low morphine requirement (10-30mg per day). Patients unable to make a self-evaluation, and patients receiving oncologic treatment were excluded. The Visual Analog Scale (VAS) was used to rate pain prior to sCT treatment and after 12hrs, 24hrs, 48hrs, and 7 days. Beta-endorphin levels were measured by radioimmunoassay at the same times along with blood counts and serum chemistries including calcium and protein levels on the 7th and 14th days.

The results of this pilot study revealed a significant reduction in pain at all time intervals with an 85% (18 of 22) reduction of pain intensity as measured by VAS from an initial mean baseline value of 4.43 to a mean of 1.5 after 7 days. Rescue medication consisting of Tylenol® and/or increased subcutaneous morphine was required by 4 patients. Additionally, pain reductions correlated with a statistically significant increase in beta-endorphin levels at all time intervals. Reduced serum calcium levels were seen on the 7th and 14th days after sCT administration; however, no significant differences were found in other laboratory parameters.

These results are promising in that sCT may serve as a useful adjuvant in the management of pain due to advanced cancer; however, several issues need to be clarified. From a theoretical perspective, it would be interesting to know whether other agents that lower serum calcium have a similar effect, and whether the duration of symptom relief correlates with the elevated levels of beta endorphin and/or the reduced serum calcium level. Additionally, a larger sample size trial with a vehicle control group would yield increased power and validity to these findings. Nevertheless, the implications of this pilot trial contribute to our limited armamentarium in the fight against pain.