Giovambattista Zeppetella

The management of cancer-related breakthrough pain: recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland.

A task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland (APM) was convened to produce some up‐to‐date, evidence‐based, practical, clinical guidelines on the management of cancer‐related breakthrough pain in adults. On the basis of a review of the literature, the task group was unable to make recommendations about any individual interventions, but was able to make a series of 12 recommendations about certain generic strategies. However, most of the aforementioned recommendations are based on limited evidence (i.e., case series, expert opinion). The task group also proposed a definition of breakthrough pain, and some diagnostic criteria for breakthrough pain.

Prevalence and Characteristics of Breakthrough Pain in Cancer Patients Admitted to a Hospice

A prospective survey was undertaken to determine the prevalence and characteristics of breakthrough pain in cancer patients admitted to a hospice. Of 414 consecutive admissions, 33 patients were confused or too unwell to take part and 136 were pain-free. The remaining 245 reported 404 pains (range 1-5 per patient); of these patients, 218 (89%) had breakthrough pain and identified 361 pains (range 1-5 per patient). Breakthrough pain was classified as somatic (46%) visceral (30%), neuropathic (10%) or mixed etiology (16%). Thirty-eight percent of pains were severe or excruciating. The average number of daily breakthrough pain episodes was 4 [corrected] (range 1-14); 49% occurred suddenly. Most (59%) were unpredictable, and 72% lasted less than 30 minutes. Seventy-five percent of patients were dissatisfied with their pain control. Breakthrough pain is common among patients admitted to our hospice. It is frequent, short lasting, often unpredictable and not necessarily related to chronic pain making treatment difficult.

Opioids for Cancer Breakthrough Pain: A Pilot Study Reporting Patient Assessment of Time to Meaningful Pain Relief

Breakthrough pain is a common and distinct component of cancer pain that is usually managed with normal release opioids (also known as rescue medication) either before or soon after its onset. A prospective survey of hospice inpatients with breakthrough pain was undertaken to characterize their pain and then compare the time to onset of pain relief of their rescue medication. Patients presented with, on average, 1.7 different types of breakthrough pains (range, 1-4). The average number of breakthrough pains was four per day (range, 1-8), and the average duration of breakthrough pain was 35 minutes (range, 15-60); most occurred suddenly and unpredictably. Patients used morphine, oxycodone, hydromorphone, methadone, or oral transmucosal fentanyl citrate as rescue medication and the average time to meaningful pain relief following their administration was 31 minutes (range, 5-75). No difference was found between morphine, oxycodone, and hydromorphone. Methadone appeared to work faster than morphine (P<0.01) but no faster than oxycodone or hydromorphone, whereas oral transmucosal fentanyl citrate worked faster than morphine, oxycodone, hydromorphone, and methadone (P<0.001).

Multi-centre European study of breakthrough cancer pain: Pain characteristics and patient perceptions of current and potential management strategies

This study involved 320 cancer patients from four Northern European countries. Patients with breakthrough pain were questioned about the characteristics of their pain, the current management of their pain, and the acceptability/utility of alternative routes of administration.

Analgesic efficacy of morphine applied topically to painful ulcers.

The analgesic effects of morphine applied topically to painful ulcers was assessed in a randomized, double-blind, placebo-controlled, crossover pilot study of five patients with painful sacral sores. Patients were treated for two days with either 10 mg morphine sulfate or placebo (water for injection) applied topically to the ulcer. After a two-day wash-out period, patients were crossed over for a further two days of the alternative treatment. Patients were asked to rate analgesia using a visual analogue scale (VAS) and to document any local or systemic adverse effects. All patients reported lower VAS scores with morphine compared to placebo and no local or systemic adverse events attributable to morphine were noted by either patients or nursing staff. This pilot study suggests that morphine applied topically is an effective method of producing local analgesia, well tolerated by patients, and not associated with systemic adverse effects.

An assessment of the safety, efficacy, and acceptability of intranasal fentanyl citrate in the management of cancer-related breakthrough pain: a pilot study.

The effects of intranasal fentanyl citrate (INFC) were assessed in 12 hospice inpatients with cancer-related breakthrough pain. Patients received 20 microg of fentanyl citrate and were asked to rate their pain using a visual analogue scale (VAS) before INFC, then after 3, 5, 10, 15, 30, 45, and 60 minutes. Eight patients (66%) had reductions in pain scores, four within 5 minutes and seven within 10 minutes of taking INFC. Ratings for INFC were very good (5 = 42%), good (3 = 25%), moderate (1 = 8%), and bad (3 = 25%). In comparison to oral morphine, INFC was better (6 = 50%), the same (3 = 25%), or worse (3 = 25%). Nine patients (75%) said they would continue to use INFC. Of the three patients who did not experience a positive result, two were taking relatively higher baseline opioid doses and one was found to have a fracture. No systemic adverse events were noted; two patients reported nasal itching or discomfort on first use that disappeared with repeated use. Intranasal fentanyl citrate appears safe and well tolerated by these patients. Randomized placebo-controlled and dose-ranging studies are required to confirm these findings.

A Network Meta-Analysis of the Efficacy of Opioid Analgesics for the Management of Breakthrough Cancer Pain Episodes

CONTEXT With many medications available for the management of breakthrough cancer pain (BTCP), physicians may require additional guidance in selecting an appropriate medication to suit an individual patients needs. OBJECTIVES To identify all the evidence and assess the relative clinical value of currently approved BTCP medications. METHODS Following a systematic literature search (2007-2010), the results of 10 randomized controlled trials investigating the effects of BTCP medications (intranasal fentanyl spray [INFS], fentanyl pectin nasal spray, fentanyl sublingual tablets, fentanyl buccal soluble film, fentanyl buccal tablets, oral transmucosal fentanyl citrate, and morphine sulfate immediate release) were synthesized using a network meta-analysis. The main outcome was pain intensity difference (PID) relative to placebo up to 60 minutes after the intake of medication. RESULTS INFS, fentanyl pectin nasal spray, fentanyl buccal tablet, and oral transmucosal fentanyl citrate showed greater PIDs relative to placebo than other BTCP medications 15 minutes after intake. All other medications showed greater PIDs relative to placebo at 30 minutes, except morphine sulfate immediate release, which did not show efficacy over placebo until 45 minutes. Only INFS produced clinically meaningful pain relief (absolute PID ≥2) at 15 minutes. CONCLUSION From current evidence, although all BTCP medications provided pain relief within the time frames assessed, transmucosal fentanyl medications achieved a greater level of pain relief in a shorter time frame than placebo or oral morphine.

Opioids for the management of breakthrough cancer pain in adults: A systematic review undertaken as part of an EPCRC opioid guidelines project

The usual management of cancer related breakthrough pain is with supplemental doses of analgesics (commonly opioids) at a dose proportional to the total around-the-clock opioid dose. The aim of this review, undertaken as part of a European Palliative Care Research Collaborative (EPCRC) project, to update the EAPC guidelines on opioid analgesics in cancer pain was to determine the evidence for the utility of opioids in the management of breakthrough pain in patients with cancer. Randomized controlled trials of opioids used as rescue medication were identified using electronic search strategies. Outcome measures sought were reduction in pain intensity measured by an appropriate scale, adverse effects, attrition, and patient satisfaction. The date of the final search was 31 July 2009. Eight studies (790 patients) met the inclusion criteria. Most studies investigated rescue medication delivery via the buccal or nasal transmucosal routes. Intravenous morphine has been compared with the transmucosal route and the two found to be effective. The oral route has not been formally tested although found to be an inferior comparator in one study. Most studies showed no meaningful relationship between the effective dose of transmucosal opioid and the around-the-clock scheduled medication or the previous rescue medication, although one study found a fixed proportion of either intravenous morphine or transmucosal fentanyl to be efficacious.

Pharmacotherapy of cancer-related episodic pain

Episodic pain is a transient increase in pain intensity over background pain. Episodic pain occurs commonly in cancer patients; it is a heterogeneous phenomenon that is incapacitating, debilitating and can have a significant impact on quality of life. Episodic pain can be difficult to manage; it is often unpredictable, typically of fast onset, of short duration and feels similar to background pain except that it may be more severe. The successful management of episodic pain can only be achieved following a thorough assessment. The subsequent management usually involves both pharmacological and non-pharmacological strategies integrated into the overall care and appropriate for the stage of the patient’s disease. Pharmacological management includes the implementation of primary therapies (e.g., chemotherapy for the underlying aetiology of the pain, optimising the scheduled medication (e.g., analgesics and adjuvant analgesics) and specific pharmacological interventions for the episodic pain (e.g., rescue medication).

Prevalence and characteristics of breakthrough pain in patients with non-malignant terminal disease admitted to a hospice:

A prospective survey was undertaken to determine the prevalence and characteristics of breakthrough pain in patients with non-malignant terminal disease admitted to a hospice. Of the 78 admissions surveyed, 10 patients were confused or too unwell to take part and 25 were pain-free. The remaining 43 reported 86 pains (range 1–6 per patient); of these patients, 27 (63%) had breakthrough pain and identified 52 pains (range 1–5 per patient). Breakthrough pain was classified as somatic (46%) visceral (14%), neuropathic (25%) or mixed aetiology (15%); 60% of pains were severe or excruciating. The mean number of daily breakthrough pain episodes was five (range 1–13), 54% of which occurred suddenly. Most pains (56%) were unpredictable; 75% lasted less than 30 min. These findings suggest that breakthrough pain is common in patients with non-malignant terminal disease; it is frequent, short lasting and often unpredictable, thus making treatment difficult.