Cevimeline for the treatment of postirradiation xerostomia in patients with head and neck cancer.
OBJECTIVE
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
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.


CONCLUSIONS
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.
Chambers
Mark S
MS
Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. mchamber@mdanderson.org
Posner
Marshall
M
Jones
Christopher Uwe
CU
Biel
Merrill A
MA
Hodge
Kenneth M
KM
Vitti
Robert
R
Armstrong
Ingrid
I
Yen
Cindy
C
Weber
Randal S
RS
D004311:Double-Blind Method; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D011812:Quinuclidines / Q000009:adverse effects / Q000627:therapeutic use*; D012472:Salivation / Q000187:drug effects / Q000502:physiology; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D014987:Xerostomia / Q000188:drug therapy* / Q000209:etiology*
D018727:Muscarinic Antagonists; D011812:Quinuclidines; D013876:Thiophenes; C059240:cevimeline