Lack of Comparative Data for Rapid-Acting Opioids Impedes Finding Optimal Treatment for Cancer-Related BTP

AUSTIN, TX—A literature review to determine comparative effectiveness of dosage forms of rapid-onset opioids used to treat cancer-related breakthrough pain (BTP) was presented at the American Pain Society's 30th Annual Scientific Meeting. Researchers found a gap in knowledge regarding this pharmacotherapy, but said the analysis does contribute to the understanding of cancer-related BTP.

Using the search string “[(breakthrough pain AND cancer) AND (randomized clinical trial OR cohort OR case-control OR pharmacotherapy)],” Hitesh Chandwani and Scott Strassels, PhD, from the University of Texas at Austin, searched PubMed, CINAHL, the Cochrane Library, and the Cochrane Central Register of Controlled Trials to identify studies of rapid-onset opioids for cancer-related BTP in humans. Hand-searching of bibliographies of papers identified additional relevant studies; excluded were meeting abstracts, letters to the editor, treatment guidelines or recommendations, expert opinions, and narrative reviews.

The search revealed three studies that compared different dosage forms of the same rapid-onset opioid: two on fentanyl and one on morphine. In the first study, a multicenter, open-label, randomized, crossover trial in 139 patients of oral transmucosal fentanyl citrate (OTFC) and intranasal fentanyl spray (INFS), INFS provided faster pain relief—a median of 11 vs. 16 minutes—and was preferred by more patients (P <0.001), resulting in ≥33% reduction in pain intensity 5 minutes after treatment initiation vs. OTFC (25.3% vs. 6.8% of cases; P<0.001).

The second study was a double-blind, placebo-controlled, crossover, randomized trial of OTFC in a sweetened matrix vs. OTFC in a compressed powder formulation in 14 patients with head and neck cancer with radiation-induced oral mucositis. The investigators found no difference in pain outcomes (time to maximum effect, maximum effect, and tolerability of drug product), between the two dosage forms.

Effervescent (EM) and immediate-release morphine sulphate (IRMS) were compared in the third study identified by the search. Within-group pain intensity scores were found to be statistically significantly reduced from baseline pain with both preparations (EM: 7.8/10 to 3.2/10, P<0.001; IRMS not shown).

Hitesh Chandwani and Dr. Strassels state that no definitive conclusions can be made about comparative effectiveness of different rapid-acting opioid dosage forms due to a dearth of such studies. Additionally, of the three that were found, two were limited due to sample size. They conclude that the lack of comparative effectiveness studies impedes the understanding of optimal treatment approaches for cancer-related break through pain. The literature review was supported in part by Meda Pharmaceuticals.