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

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.