Pilot dose finding study of intranasal sufentanil for breakthrough and incident cancer-associated pain

Background
Up to 60% of patients with cancer-associated pain suffer from episodes of breakthrough or incident pain. The standard management of this is bolus oral or subcutaneous administration of an immediate release opioid, usually morphine. However, this does not meet the ideal characteristics of a breakthrough drug, which are: rapid onset, early peak effect and duration of action of 1-2 hours. In post operative care the problem is often overcome using an intravenous patient controlled analgesia (PCA) device but this has not found favour in the palliative care setting.

The sublingual (SL)' and intranasal (IN) routes are both being re-explored as they avoid first pass effect metabolism, allow for rapid absorption by an area with a rich blood supply and are not painful to administer. Plasma concentrations obtained at 30 minutes are equivalent to those achieved after intravenous administration. The physico-chemical properties of sufentanil and the concentration of the commercially available formulation suggest that it may be the most suitable of the available opioids for use by this route.

A commercially available patient controlled intranasal analgesia (PClNA) spray device manufactured by GO MedicalTM delivers 0.18ml as a fine spray to the nasal mucosa thus mimicking the efficacy of intravenous PCA} This device is therefore being evaluated in an open label pilot study in an acute palliative care inpatient unit, to demonstrate the efficacy, safety, and patient and staff acceptance, of intranasal sufentanil for this indication.

Methods
Patients and procedure

1. Non-opioid naive inpatients in the palliative care or oncology wards requiring breakthrough analgesia
2. Daily dose escalation if required to a maximum of 3 doses of 36mctg
3. One nurse to have sole responsibility for each individual episonde
4. All other medications continued unchanged, except that once or more per day, the patient may be given intranasal sufentanil instead of their usual breakthrough opioid medication.

Dose escalation

Step 1
4.5mcg dose, which may be repeated at 10 minutes and 20 minutes if required and drowsiness scale less than 2. If effective, this dose may be continued. If ineffective at 30 minutes, give usual opioid breakthrough and go to Step 2 on next or subsequent day;

Step 2
Start with a 9mcg dose, then as above;

Step 3
Start with a 18mcg dose, then as above;

Step 4
Start with a 36mcg dose, then as above;

Assessment Tools
Verbal response (VRS) pain and drowsiness scores, respiratory rate and SPO2 are collected for 2 hours after first dose of each episode. Each episode to be analysed individually for response, time to response, adverse effects if any, and patient preference, as compared to the usual breakthrough medications.

Results
The study is still accruing. In 5 out of 7 episodes good pain relief occurred within 10 minutes and lasted about 2 hours. These patients rated IN sufentanil as much better than their usual opioid breakthrough, both in speed of onset and efficacy. No episode was associated with drowsiness, nausea/vomiting or respiratory depression.

Associated Publication(s):
Jackson K, Ashby M, Keech J. Pilot dose finding study of intranasal sufentanil for breakthrough and incident cancer-associated pain. Journal of Pain and Symptom Management 2002 Jun; 23(6): 450-2