Breakthrough cancer pain: twenty-five years of study

Breakthrough cancer pain (BTcP) is an episode of severe pain that "breaks through" a period of persistent pain at least partly controlled by a stable opioid regimen. Although mentioned in the literature decades ago, it has been only 25 years since the first effort to define and measure it. Controversy about the definition of BTcP continues despite an international effort to achieve consensus. Nevertheless, common approaches to measurement of BTcP have led to a robust literature, including many surveys that have described prevalence, characteristics, and association with adverse outcomes. Measurement also has been important for clinical trials of new drug formulations specifically designed for BTcP. Several approaches have been reported in the literature, although most of them have never been substantiated with appropriate studies. Administration of an opioid as needed is the most common treatment. Twenty-five years of research has produced a more refined understanding of the safety and efficacy of oral opioids in this context, and provided the clinical trials data necessary to attain regulatory approval of multiple new formulations specifically developed for BTcP. Transmucosal formulations of fentanyl may provide meaningful analgesia within 5 to 15 minutes. Given the difference in cost, transmucosal formulations should be considered in a subset of patients with BTcP, including those with pain that are not adequately controlled with an oral drug and those with distress associated with the rapid pain onset. The long-term use of opioids for BTcP remains to be clarified. Future studies should assess the potential of personalized treatment of BTcP.