New therapy options for breakthrough pain

A series of therapeutic innovations introduced at the EAPC Congress should further improve medical provisioning of palliative patients in matters of symptom control. A serious problem involving cancer patients is so-called "breakthrough pain": this is an instantaneous intensive sharp pain, additional to "all-over" dull pain, that usually lasts only a half-hour to one hour and reaches its highest intensity some minutes after the outbreak. More than 85 percent of cancer patients suffer from this form of pain. It is enormously burdensome for palliative patients and particularly difficult to control, because the unpredictable breakthrough attacks require an enormously rapid effectiveness of the analgesic, something many agents and forms of medication cannot provide. The full effect of conventional orally administered opioids is achieved only about 35 to 45 minutes after intake – much too late to deal with the breakthrough pain.

"Several new and efficient possibilities for the struggle against breakthrough pain will be presented at the EAPC Congress," Professor Kress noted.  

Rapid pain alleviation through the nose

The Vienna University Clinic for Anesthesia had intensively participated in the research on new therapeutic options that should be given official approval soon. Professor Kress, together with colleagues from several European countries, are thus presenting new, hitherto unpublished data from several multicentre studies in which the effectiveness and tolerance of fentanyl nasal spray was analysed in connection with cancer patients with breakthrough pain.

The administering of fentanyl opioids through the nose has proven itself as a good alternative to oral or intravenously administered medication because the substance can be quickly absorbed through the mucosa tissue and is therefore convenient for patients who suffer from difficulty in swallowing, very dry mouth or nausea and vomiting.

A few pivotal results: a short delivery time – clinically relevant plasma levels are already observed two minutes after administering the medication – make the new therapy option especially suitable for breakthrough pain. Strengths of 50, 100 and 200 micrograms were examined.

"We were able to notice a very rapid effectiveness. Initial clinically relevant fentanyl plasma concentrations were already observed two minutes after administering the drug. A meaningful pain reduction of at least two points on the eleven point numerical rating scale occurred ten minutes after application in most of the patients. The nasal spray therewith turned out to be a good option for breakthrough pain."

Professor Kress further: "It was well tolerated by the patients in all of the dosages administered in our studies."

Buccal tablets

Other new galenics for fentanyl administration will also be presented at the EAPC Congress. One involves a new buccal tablet, likewise shown to provide rapid effectiveness. It has been approved in the US and will soon be available in Europe. The concept is a fentanyl effervescent tablet: it is placed between upper jaw and inside cheek, so that carbon dioxide is freed as it dissolves, further promoting absorption of the substance. "Studies have shown that with the buccal tablet a significantly stronger pain reduction is achieved than with a placebo," Prof. Kress comments.

Similar results are held for sublingual tablets, in which micronized fentanyl in fine particle sizes are released upon contact with saliva. Professor Kress: "Here too, studies have shown significant pain reduction within ten minutes of intake."

Combination medicament against constipation

Another hitherto insufficiently resolved problem in palliative medicine: opioids are a potent pain reliever, of course, but side effects such as constipation can burden the patient enormously. According to a survey conducted in the US and Europe, 81% of patients using opioids on a regular basis suffer from obstipation.

"At the Congress we’ll be dealing with, among other things, a new oxycodone-naloxone combination preparation that hinders blockage in the bowels," Professor Kress says.

A trial showed that among patients using the oxycodone-naloxone combination, only 31% needed a laxative; in the group of patients using oxycodone only, this rate was at 55,1%.

Oxycodone is a strong opioid; naloxone an opioid antagonist. The latter has the task of blocking the opioid receptors in the intestinal wall that inhibit oxycodone from binding with them. The analgesic effect of the oxycodone is not adversely affected.

Cannabinoid with multiple usages in palliative medicine

Finally, an important theme in connection with this will also be the use of cannabinoids in palliative medicine.

"There is increasingly more data, meanwhile, indicating that cannabinoids are practical as a co-analgesic when other co-analgesics showed insufficient effect or when they had to be withdrawn on account of their-side effect profile," according to Professor Kress.

"In palliative care, cannabinoids are therefore also interesting because they exhibit a broad active profile far in excess of the analgesic."

In the coming year a commercial drug with the THC dronabinol is anticipated that should make adoption significantly easier than is currently allowed by single-order limitations in the pharmacy.

One study out of Klagenfurt being presented at the Congress examines the effect of 2.5% drops of the dronabinol cannabinoid on nausea, vomiting and appetite loss. The initial dosage was 2.5 milligrams twice daily that could be increased to five or ten milligrams in cases of insufficient symptom alleviation. Result of the investigation: in the case of nausea, some modest improvement was achieved; regarding vomiting incidents, a significant reduction. Incidents of appetite loss could likewise be reduced substantially. Side-effects at these dosages were not observed.

(Source: European Association for Palliative Care: May 2009)