Article of the Month

Efficacy and Tolerability of Intranasal Fentanyl Spray 50 to 200 ug for Breakthrough Pain in Patients With Cancer: A Phase III, Multinational, Randomized, Double-Blind, Placebo-Controlled, Crossover Trial With a 10-Month, Open-Label Extension Treatment Period

Kress HG, Oronska A, Kaczmarek Z,et al. Clinical Therapeutics 2009;32 (6):1177-91

The aim of this randomized double blind, cross-over study was to evaluate the efficacy and tolerability of an intranasal fentanyl spray (from 50 to 200 μg), vs intranasal placebo in treating breakthrough pain (BP) in opioid tolerant hospitalized cancer patients in five European countries.

The main end point of the study was to assess the pain intensity difference after 10 minutes of the drug/placebo administration, using the Numerical Rating Scale (no pain = 0 and worst pain= 10) that considers clinically relevant a difference of 2 points.

The inclusion criteria were:

• a life expectancy ≥ 3 months,

• at least 3 episodes/week of BP lasting > 15 minutes with a maximum of 4 episodes/day, and
• responsivity (at least partial) to opioids previously administered for BP. The patients treated with buprenorphine or methadone on a regular basis were not included in the study.

The study was carried out in 120 patients included in a “run in” initial phase to determine the analgesic doses of the intranasal fentanyl.

One hundred and eleven patients were randomized and evaluated (mean age 61; 50% male). All the patients had been treated with fentanyl (54%) or morphine (43%) for one month. The RCT lasted 3 weeks in which 4 daily administrations, as a maximum, of intranasal fentanyl or placebo were administered. Then an open study continued for 10 months to assess the long term tolerability of the doses of fentanyl found useful in relieving BP episodes.

43% of the patients were treated with 100 µg of fentanyl and 41% of the patients with a dose of 200 µg; 5% of the patients had to stop the fentanyl due to severe adverse effects.

51% of the patients treated with fentanyl vs 21 % of the patients the placebo had a clinical reduction in pain intensity of 2 points. 58% of patients on fentanyl vs 28% of patients treated with placebo had a pain reduction of more than 30%.

The mean variation in the pain intensity score after 10 minutes (main endpoint) was 2.4 with intranasal fentanyl and 1.1 with placebo. These data are significantly different, but not significantly relevant from a clinical point of view.

Why I chose this article

Data from the literature related to the frequency of BP vary widely. Sometimes BP is erroneously confused with other types of episodic pains such as “final dose analgesic” pain or “movement related” pain. For this reason it is important to further investigate the semantic etiology and the epidemiology of BP. Many short acting opioids have been proposed for the treatment of BP.

Kress et al. present the first RCT assessing the efficacy and tolerability of intranasal fentanyl in oncological patients with BP. Unfortunately only the patients included in the “run in “ phase were evaluated. Moreover the drug was only compared to a placebo and not to short release morphine, subcutaneous or intravenous morphine or transmucosal fentanyl (lollipop).

Further investigation is necessary regarding the efficacy and the tolerability of intranasal fentanyl for BP for hospitalized patients as well as those cared for in ambulatory and in-home care settings

Please visit www.ceveas.it

Carla Ripamonti, MD (Italy)

Dr. Ripamonti is a member of the IAHPC Board of Directors; her bio may be viewed at: http://www.hospicecare.com/Bio/c_ripamonti.htm