Opioid Resistance Score May Be Useful for Stratifying Patients With Cancer Pain

The resistance score (RS) was found to be a sensitive predictor for opioid resistance in patients experiencing cancer pain, according to the results of a study published in the Journal of Pain & Palliative Care Pharmacotherapy.

At team of investigators from Tokyo, Japan, conducted a historical cohort study between 2005 and 2011 at the Palliative Care Center of Showa University Hospital. Patients (N=233) with moderate to severe pain that had been treated with morphine or oxycodone and who had undergone an observation period of at least 2 weeks were included. Pain intensity was assessed using a 10-point numeric rating scale. The primary outcome was achieving stable pain — defined as daily pain rated as mild — by day 14 following opioid administration. Opioid responders (n=184) and those resistant (n=49) were subdivided and evaluated for resistance predictors.

The response and resistance cohorts were aged mean 67.2±12.0 and 61.3±13.7 years (P =.004), 58.7% and 42.9% were men (P =.047), 44.0% and 67.3% had neuropathic pain (P =.004), 81.0% and 77.6% had metastatic disease, 48.4% and 34.7% had gastrointestinal cancer, 23.9% and 20.4% had gynecological cancer, 15.8% and 18.3% had urologic cancer, 12.0% and 26.5% had respiratory cancer, and 40.2% and 36.7% were receiving palliative care, respectively.

Morphine was administered to 54.5% of patients, and oxycodone was administered to 45.5% of patients; 59.2% of patients received opioid treatment in oral form at a mean dose of 20.8±11.1 mg of oral morphine equivalent.

Multivariate analysis revealed predictors of resistance to include neuropathic pain (odds ratio [OR], 3.047; 95% CI, 1.357-6.844; P =.007), alkaline phosphatase (ALP) per log₁₀ increase (OR, 0.159; 95% CI, 0.033-0.765; P =.022), and age per 10-year increase (OR, 0.715; 95% CI, 0.527-0.968; P =.030).

Using these factors, the RS was calculated as:

RS = 0.336×(age×1/10)-1.114×(neuropathic pain: yes=1, no=0)+1.841×(log[ALP]) -4.877

An RS less than 1.8, reflecting high risk for opioid resistance, had a sensitivity of 80.6%. The negative predictive value for opioid response in the low-risk group — those with an RS ≥1.8 — was 91.6%.

The duration of time to achieve stable pain was longer among the high-risk cohort (median, 7 vs 4 days; P <.001).

The major limitation of this study was not evaluating the RS among an independent cohort.

This study found that younger age, neuropathic pain, and low ALP level are risk factors for opioid resistance, and the investigators used these parameters to formulate the RS. This tool may be useful in evaluating potential resistance before initiating opioids among patients with cancer pain. The researchers concluded, “The application of these results to common practice may lead to the selection of appropriate treatment and the prevention of unnecessary opioid escalation, and will contribute to the support of cancer pain management.”