Purpose: To study the efficacy and safety of cevimeline in two double-blind trials (Studies 003 and 004) enrolling patients with head and neck cancer in whom xerostomia developed after radiotherapy. Methods and Materials: Subjects were randomly assigned to receive cevimeline, 30 mg three times daily, or placebo for 12 weeks, with the possibility of dose escalation to 45 mg three times daily at 6 weeks. The primary efficacy endpoint was the patient's final global evaluation of oral dryness; change in unstimulated salivary flow was a secondary endpoint. Results: Five hundred seventy subjects (284 in Study 003 and 286 in Study 004) were randomized. Significantly more cevimeline-treated subjects than placebo recipients (47.4% vs. 33.3%, p = 0.0162) in Study 003 reported improvement in dry mouth in the final global evaluation of oral dryness. No significant difference between groups in the final global evaluation was seen in Study 004, in which a high placebo response rate of 47.6% was observed. In both studies, cevimeline-treated subjects had significantly greater increases in the objective measure of unstimulated salivary flow than placebo recipients (p = 0.0093 [Study 003] and p = 0.0215 [Study 004]), whereas no significant differences in stimulated salivary flow were observed. The most frequent adverse event was increased sweating. Conclusion: Cevimeline was well tolerated by patients with xerostomia after radiotherapy for head and neck cancer, and oral administration of 30-45 mg of cevimeline three times daily increased unstimulated salivary flow.
|Original language||English (US)|
|Number of pages||8|
|Journal||International Journal of Radiation Oncology Biology Physics|
|State||Published - Jul 15 2007|
Bibliographical noteFunding Information:
Conflict of interest: M.S.C. has received research grant support from RxKinetix, Inc., Daiichi Sankyo, Inc., the National Institute of Dental and Craniofacial Research, and MedImmune, Inc., and serves on the speakers’ bureau for Daiichi Sankyo, Inc., and is a consultant for Nuvelo, Inc. M.P. has received research grant support from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, MedImmune, Inc., Genentech, Aventis-Sanofi, AstraZeneca, Bristol-Myers Squibb, OSI Pharmaceuticals, Amgen, Viventia Biotech Inc., and Millennium Pharma; M.P. has also served as a consultant to the National Cancer Institute, Amgen, Milenix, and GlaxoSmithKline. R.V. and C.Y. were employees of Daiichi Pharmaceutical Corporation while studies 003 and 004 were being carried out. I.A. is an employee of Daiichi Sankyo, Inc. R.S.W. reports having received travel grant support from Daiichi Pharmaceutical Corporation in 2004 for a scientific presentation.
Copyright 2009 Elsevier B.V., All rights reserved.
- Dry mouth
- Head-and-neck cancer
- Postirradiation xerostomia