The use of rapid onset opioids for breakthrough cancer pain: The challenge of its dosing

Abstract

Breakthrough cancer pain (BTcP) has been defined as a transitory increase in pain intensity on a baseline pain of moderate intensity in patients on analgesic treatment regularly administered. This review provides updated information about the use of opioids for the treatment of BTcP, with special emphasis on the use of new rapid onset opioids (ROOs).

Due to its slow onset to effect oral opioids cannot be considered an efficacious treatment for BTcP. Parenteral opioids may provide rapid onset of analgesia, but not always available particularly at home. Different technologies have been developed to provide fast pain relief with potent opioid drugs such fentanyl, delivered by non-invasive routes. Transmucosal administration of lipophilic substances has gained a growing popularity in the last years, due to the rapid effect clinically observable 10–15 min after drug administration, obtainable in non-invasive forms. Fentanyl is a potent and strongly lipophilic drug, which matches the characteristics to favour the passage through the mucosa and then across the blood–brain barrier to provide fast analgesia. Transmucosal, buccal, sublingual, and intranasal fentanyl showed their efficacy in comparison with oral morphine or placebo and are available for clinical use in most countries. All the studies performed with ROOs have recommended that these drugs should be administered to opioid-tolerant patients receiving doses of oral morphine equivalents of at least 60 mg. The choice of the dose of ROO to be prescribed as needed remains controversial. The need of titrating opioid doses for BTcP has been commonly recommended in all the controlled studies, but has never been substantiated in appropriate studies.

Introduction

Patients with cancer pain often present with fluctuations in pain intensity. Breakthrough cancer pain (BTcP) has been defined as a transitory increase in pain intensity on a baseline pain of moderate intensity in patients on analgesic treatment regularly administered [1]. Patients are often receiving basal medication for their pain which is otherwise considered acceptable. Although highly variable, BTcP is typically rapid in onset, moderate to severe in intensity, and relatively short in duration [2]. Three principal categories of BTcP have been identified: (a) spontaneous pain with no evident precipitating event; (b) incident pain, with an evident precipitating cause or event, for example due to activity; (c) end of dose failure, associated with therapeutic holes due to a reduction in blood analgesic levels of medications provided at regular intervals. The latter group does not exactly corresponds to the definition of BTcP, expressing a status of inappropriate analgesia, although from a clinical perspective it still represents a clinical problem to be addressed as BTcP. Another way to classify BTcP could be based on the presence of volitional or precipitant factors, which have been identified in more than 50% of patients. Therefore, for each category different subtypes can be also identified.

Previous surveys have found that this phenomenon, is highly prevalent among patients with cancer pain and predicts more severe pain, pain-related distress and functional impairment, and relatively poor quality of life [2]. In different surveys 50–90% of cancer patients with pain have been reported to experience intermittent flares of their pain, although using different definitions and methodology [1], [2], [3], [4], [5]. These figures have been confirmed in a large international survey assessing the prevalence of BTcP, showing a prevalence of about 65% [6].

Pharmacological treatment regimes are based on implementation of primary therapies, optimization of scheduled analgesia [7], and specific treatment of BTcP [2], [3]. The aim of this review is to provide updated information about the use of opioids for the treatment of BTcP, with special emphasis on the use of new rapid onset opioids (ROOs).