Open-label, long-term safety study of cevimeline in the treatment of postirradiation xerostomia.
OBJECTIVE
To assess the safety of long-term cevimeline treatment of radiation-induced xerostomia in patients with head-and-neck cancer; and to assess the efficacy of cevimeline in these patients.


METHODS
A total of 255 adults with head-and-neck cancer who had received more than 40 Gy of radiation 4 months or more before entry and had clinically significant salivary gland dysfunction received cevimeline hydrochloride 45 mg t.i.d. orally for 52 weeks. Adverse events (AEs), their severity, and their relationship to the study medication were assessed by each investigator. The efficacy assessment was based on subjects' global evaluation of oral dryness on a scale of 0 (none) to 3 (severe).


RESULTS
Overall, 175 subjects (68.6%) experienced expected treatment-related AEs, most mild to moderate. The most frequent was increased sweating (47.5%), followed by dyspepsia (9.4%), nausea (8.2%), and diarrhea (6.3%). Fifteen subjects (5.9%) experienced Grade 3 treatment-related AEs, of which the most frequent was increased sweating. Eighteen subjects (7.1%) reported at least one serious AE, and 45 subjects (17.6%) discontinued study medication because of an AE. The global efficacy evaluation at the last study visit showed that cevimeline improved dry mouth in most subjects (59.2%). Significant improvement was seen at each study visit in the mean change from baseline of the numeric global evaluation score (p < 0.0001).


CONCLUSIONS
Cevimeline 45 mg t.i.d. was generally well tolerated over a period of 52 weeks in subjects with xerostomia secondary to radiotherapy for cancer in the head-and-neck region.
Chambers
Mark S
MS
Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. mchamber@mdanderson.org
Jones
Christopher Uwe
CU
Biel
Merrill A
MA
Weber
Randal S
RS
Hodge
Kenneth M
KM
Chen
Y
Y
Holland
John M
JM
Ship
Jonathan A
JA
Vitti
Robert
R
Armstrong
Ingrid
I
Garden
Adam S
AS
Haddad
Robert
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003967:Diarrhea / Q000139:chemically induced; D004415:Dyspepsia / Q000139:chemically induced; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D009325:Nausea / Q000139:chemically induced; D011812:Quinuclidines / Q000008:administration & dosage / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D013542:Sweat / Q000187:drug effects; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects*; D014987:Xerostomia / Q000188:drug therapy*
D018721:Muscarinic Agonists; D011812:Quinuclidines; D013876:Thiophenes; C059240:cevimeline