Dose titration of fentanyl pectin nasal spray in a broad range of patients for the treatment of breakthrough pain in cancer.

Abstract

e19659 Background: Randomized controlled studies have demonstrated that fentanyl pectin nasal spray (FPNS) provides superior pain relief compared with placebo and immediate-release morphine sulfate for the treatment of patients with breakthrough pain in cancer (BTPc). An ideal BTPc agent should also be easily titratable across a wide range of patient types. This report details the successful dose titration of FPNS in the clinical trial program. Methods: The FPNS clinical trial program enrolled 523 patients experiencing 1–4 BTPc episodes/day while taking ≥60 mg/day oral morphine (or equivalent) for background pain. The open-label titration phase was designed to find an effective dose that successfully treated 2 consecutive episodes of BTPc without unacceptable adverse events (AEs). Results: Across the FPNS clinical trial program, a total of 2,417 episodes of BTPc were treated with FPNS in the dose-titration phase. This included a broad range of patient types: >28% were >60 years of age (mean age, 54.2), 48% were female, 55% were white, 56.6% had an Eastern Cooperative Oncology Group (ECOG) score = 1, and 21% were undergoing chemotherapy. Patients were successfully titrated to either 100 µg (17.7%), 200 µg (21.8%), 400 µg (32.0%), and 800 µg (28.5%) in a minimal number of steps (mean, 2.7). Successful titration was consistent across the 3 multinational, multicenter studies at sites across 13 countries and 4 continents. Dose distribution did not vary by age or by weight, although there was a slight tendency for men to titrate to higher doses. Titration failed for FPNS-related reasons in 42 (8.0%) patients: 15 (2.9%) because of AEs and 27 (5.2%) because of inadequate efficacy. Treatment-related AEs leading to withdrawal were primarily headache, nausea, and vomiting, consistent with the known effects of fentanyl; they were not dose related. Conclusions: FPNS provides an easy-to-use and convenient method of administration for the treatment of BTPc. Furthermore, FPNS is easily titrated to an effective dose in a broad range of opioid-tolerant cancer patients, with only 8.0% unable to titrate for FPNS-related reasons.