Efficacy and safety of fentanyl pectin nasal spray versus immediate-release morphine sulphate tablets in the treatment of breakthrough cancer pain.

Abstract

9016^ Background: Breakthrough cancer pain (BTCP) affects most cancer patients with pain. Immediate-release morphine sulphate (IRMS) remains the mainstay of treatment, but its onset of effect does not match the rapid onset and duration of most BTCP episodes. Fentanyl pectin nasal spray (FPNS) has pharmacokinetics that enable rapid onset of pain relief. This study assessed the efficacy of FPNS vs IRMS in the treatment of BTCP. Methods: Patients (N = 110) experiencing 1–4 BTCP episodes/day while taking ≥60 mg/day oral morphine (or equivalent) for background pain entered a double-blind, double-dummy (DB/DD), multiple-crossover study. Patients who completed a titration phase (N = 84) continued to a DB/DD phase; 10 episodes of BTCP were randomly treated with FPNS and oral capsule placebo (5) or IRMS and nasal spray placebo (5). Pain intensity (PI; 11-point scale) was measured up to 60 min. The primary endpoint was PI difference from baseline at 15 min (PID15). Secondary endpoints were onset of pain improvement (≥1-point PI decrease), time to clinically meaningful pain relief (CMPR; defined as ≥2-point decrease in PI or ≥2-point decrease in summed PID [SPID]), and patient satisfaction. Safety and tolerability were evaluated by adverse events (AEs) and nasal assessments. By-patient and by-episode analyses were completed. Results: FPNS significantly improved mean PID15 scores vs IRMS (P = 0.0396; N = 79). 740 BTCP episodes were analysed (FPNS = 372; IRMS = 368): 57.5% of FPNS-treated episodes showed onset of PI improvement by 5 min, and 95.7% showed it by 30 min (both P<0.05 vs IRMS). CMPR (≥2-point PI decrease) was seen in 52.4% of episodes by 10 min (P<0.05 vs IRMS). Similarly, at 10 min, significantly more episodes had a reduction in SPID score of ≥2, ≥3, and ≥4 points following FPNS vs IRMS (all P<0.05). Patients were satisfied/very satisfied with FPNS for 81.5% of episodes vs 71.2% with IRMS (P<0.01). Only 4.7% of patients withdrew from titration (2.4% in DB/DD phase) due to AEs; no significant nasal effects were reported. Conclusions: FPNS is efficacious and well tolerated in the treatment of BTCP. Furthermore, FPNS provided faster onset of analgesia and attainment of CMPR than IRMS. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Archimedes Archimedes Archimedes Archimedes Archimedes In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.