The Prevalence and Characteristics of Breakthrough Cancer Pain in Patients Receiving Low Doses of Opioids for Background Pain

Abstract

The aim of this study was to assess the prevalence and characteristics of breakthrough cancer pain (BTcP) in patients receiving low doses of opioids for background pain. A consecutive sample of advanced cancer patients receiving less than 60 mg/day of oral morphine equivalent (OME) was selected. Epidemiological data, background pain intensity, and current analgesic therapy were recorded. The presence of BTcP was diagnosed according to a standard algorithm. The number of BTcP episodes, intensity of BTcP, its predictability and triggers, onset duration, interference with daily activities, BTcP medications, satisfaction with BTcP medication, and time to meaningful pain relief were collected. A total of 126 patients were screened. The mean intensity of background pain was 2.71 (1.57), and the mean OME was 28.5 mg/day (SD15.8). BTP episodes were recorded in 88 patients (69.8 %). The mean number/day of BTP episodes was 4.1 (SD 7.1, range 1–30). In a significant percentage of patients, BTcP was both predictable and unpredictable (23%). The BTcP onset was less than 20 min in the majority of patients. The mean duration of untreated episodes was 47.5 (SD 47.6) minutes. The mean time to meaningful pain relief after taking a BTcP medication was >20 min in 44.5% of patients. The efficacy of BTcP medication was not considered good in more than 63% of patients. Gender (females) (OR = 4.16) and lower Karnofsky (OR = 0.92) were independently associated with BTcP. A higher number of BTcP episodes/day was associated with gender (females) (p = 0.036), short duration of BTcP (p = 0.005), poorer efficacy of BTcP medication (none or mild) (p = 0.001), and late meaningful pain relief (p = 0.024). The poor efficacy of BTcP medication was independently associated with a higher number of episodes/day (OR = 0.22). In patients who were receiving low doses of opioids, BTcP prevalence was 69.8%. Many patients did not achieve a sufficient level of satisfaction with BTcP medications, particularly with oral morphine. Data also suggest that better optimization of background analgesia, though apparently acceptable, may limit the number of BTcP episodes.

Prostate cancer induced bone pain: pathobiology, current treatments and pain responses from recent clinical trials

“…In patients, high expression levels of cyclin A1 and aromatase proteins in metastatic bone lesions support the notion that stem cell-like prostate cancer cells overexpressing cyclin A1 and aromatase, preferentially metastasize to bone [ 70 ]. Indeed, cyclin A1 and aromatase increased local production of bone marrow-releasing factors including androgen receptor, Hairy/enhancer-of-split related with YRPW motif-like protein (HeyL), oestrogen, oestrogen receptor alpha, and matrix metalloproteinase 9 (MMP9), that together facilitate metastatic homing to the bone marrow [ 51 , 70 , 90 ]. Thus, local production of steroid hormones and MMPs in the bone marrow likely contribute to generation of a microenvironment suitable for stem-like prostate cancer cells to establish metastatic lesions in bone [ 51 , 70 ].…”

“…In prostate cancer, only rare, phenotypically distinct prostate cancer tumour-initiating cells, also called stem-like prostate cancer cells, have the capacity to form new tumours [ 59 ]. However, the mechanisms leading to bone metastasis formation are not fully elucidated [ 70 ]. In patients, high expression levels of cyclin A1 and aromatase proteins in metastatic bone lesions support the notion that stem cell-like prostate cancer cells overexpressing cyclin A1 and aromatase, preferentially metastasize to bone [ 70 ].…”

“…However, the mechanisms leading to bone metastasis formation are not fully elucidated [ 70 ]. In patients, high expression levels of cyclin A1 and aromatase proteins in metastatic bone lesions support the notion that stem cell-like prostate cancer cells overexpressing cyclin A1 and aromatase, preferentially metastasize to bone [ 70 ]. Indeed, cyclin A1 and aromatase increased local production of bone marrow-releasing factors including androgen receptor, Hairy/enhancer-of-split related with YRPW motif-like protein (HeyL), oestrogen, oestrogen receptor alpha, and matrix metalloproteinase 9 (MMP9), that together facilitate metastatic homing to the bone marrow [ 51 , 70 , 90 ].…”

“…Indeed, cyclin A1 and aromatase increased local production of bone marrow-releasing factors including androgen receptor, Hairy/enhancer-of-split related with YRPW motif-like protein (HeyL), oestrogen, oestrogen receptor alpha, and matrix metalloproteinase 9 (MMP9), that together facilitate metastatic homing to the bone marrow [ 51 , 70 , 90 ]. Thus, local production of steroid hormones and MMPs in the bone marrow likely contribute to generation of a microenvironment suitable for stem-like prostate cancer cells to establish metastatic lesions in bone [ 51 , 70 ]. The bone microenvironment may also regulate metastatic prostate cancer cells between dormant and proliferative states with dormancy potentially lasting for many months if not years [ 80 , 106 ].…”

Evaluation of the clinical efficacy of oxycodone PCIA in patients with postherpetic neuralgia complicated with breakthrough pain: protocol for a prospective, double-blind, randomized controlled trial

“…The primary variables for outcome measures are response rate and incidence of adverse events following rescue analgesia. Since there are no reports on the use of oxycodone PCA for breakthrough pain rescue analgesia in PHN, we referred to previous studies related to cancer breakthrough pain [16][17][18]. The adverse reaction rates after rescue analgesia with oxycodone were 58.9% and 48.8%, respectively.…”