Circadian rhythm of breakthrough cancer pain.

Background: breakthrough pain (BTP) is a transitory flare of pain that occurs on a background of well controlled baseline pain. BTP is highly prevalent among patients with cancer pain treated with major opioids. The events of BTP are considered unpredictable, although some studies have provided preliminary data suggesting a possible circadian pattern of such events; the results are however contrasting. The aim of the present investigation was to assess the diurnal variation of BTP in two separate consecutive patient series. Methods: from December 2009 to February 2010, and from April 2010 to June 2010, two groups of consecutive patients attending a Medical Oncology Day Hospital, suffering from severe chronic pain and treated with major opioids were enrolled in the study. To each patient were administered a general pain questionnaire and the "diary of BTP", consisting in a table in which the patient could record every event of BTP, if present, for the duration of seven days, by crossing the corresponding box of day and hour. Results: In group 1 were included 47 patients, 23 M and 24 F while in group 2, 76 patients, 37 M and 39 F. The primary malignancies mostly represented were breast, colon-rectum and prostate, while the main sites of metastases were bone, liver and lymph nodes. BTP was found in 41/47 patients in group 1 and 45/76 patients in group 2. At Cosinor analysis BTP events in group 1 showed a circadian pattern, with an acrophase at 13.45. (p<0.01). In group 2 similarly a circadian pattern emerged, with an acrophase at 10.45. (p<0.001). By dividing into two subgroups, for presence or absence of bone metastases, the circadian pattern was conserved: in group 1 patients with bone metastases had an acrophase at 11.55 (p<0.05), while those without bone metastases had an acrophase at 14.30 (p<0.05); in group 2 patients with bone metastases had an acrophase at 10.45 (p<0.01), while those without bone metastases had an acrophase at 10.15 (p<0.001). Conclusions: BTP showed a circadian pattern with peak in the same phase of the day in both pilot and validation series of patients. These results suggest that BTP events may be relatively predictable, and provide a rationale for testing the efficacy of boosting doses of immediate release opioid to prevent this event.