Response to Oral Immediate-Release Opioids for Breakthrough Pain in Patients with Advanced Cancer with Adequately Controlled Background Pain

Oncologist. 2019 Jan;24(1):125-131. doi: 10.1634/theoncologist.2017-0583. Epub 2018 Sep 25.


Background: There is limited evidence about the response of breakthrough pain (BTP) to the most commonly used oral immediate-release (IR) opioids. Our aim was to determine response rate to oral IR opioids for BTP control in patients with advanced cancer.

Materials and methods: In this prospective study, palliative care outpatients, with advanced cancer and adequately managed background pain, were asked to complete a self-administered survey. We assessed patients' baseline demographics, pain characteristics, alcoholism (CAGE questionnaire), tobacco and substance abuse, and Edmonton Symptom Assessment Scores (ESAS). We determined the effectiveness of oral IR BTP opioids by using a 7-point Likert scale ranging from "very ineffective" to "very effective." "Effective" and "very effective" were defined a priori as a good response to IR opioids for BTP.

Results: Of 592 evaluable patients, 192 (32%) had background pain of ≤3 (ESAS pain scale 0-10). Among these 192 patients, 152 (79%) reported BTP, 143/152 (94%) took oral IR opioids for BTP, and 127/143 (89%) responded to a median dose of 10% of the total morphine equivalent daily dose. In univariate logistic regression analysis, younger age (odds ratio [OR], 0.94 per year; p = .008), higher ESAS scores for pain (OR, 1.32; p = .012), anxiety (OR, 1.24; p = .017), and dyspnea (OR, 1.31; p = .007) had statistically significant association with poor response to IR opioids for BTP. In multicovariate logistic regression, adjusted for age, a higher ESAS dyspnea score was significantly associated with poor response to oral IR opioids (OR, 1.44; p = .002).

Conclusion: The vast majority of patients with advanced cancer with adequately controlled background pain reported a good response to oral IR opioids for BTP, supporting their use in clinical practice.

Implications for practice: Oral immediate-release opioids are standard treatment for cancer breakthrough pain. However, information regarding treatment response to these commonly used opioids is limited. This study provides information that the vast majority of patients with advanced cancer, with adequately controlled background pain, reported good response to oral immediate release opioids for managing their breakthrough pain episodes. Results of this study support the use of conventional oral immediate release opioids that are relatively inexpensive and readily available for management of breakthrough pain in patients with advanced cancer.

Keywords: Breakthrough cancer pain; Breakthrough pain; Cancer; Episodic pain; Incidental pain; Opioid; Pain; Palliative care; Rescue medication.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Aged
  • Analgesics, Opioid / pharmacology
  • Analgesics, Opioid / therapeutic use*
  • Cancer Pain / drug therapy*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pain Management / methods*
  • Prospective Studies


  • Analgesics, Opioid