RATIONALE: Cevimeline may be effective in treating dry mouth that is caused by radiation
therapy for head and neck cancer. It is not yet known if cevimeline is more effective than
no therapy in treating dry mouth caused by radiation therapy.
PURPOSE: Randomized phase III trial to determine the effectiveness of cevimeline in treating
patients who have dryness of the mouth caused by radiation therapy for head and neck cancer.
- Compare the efficacy of cevimeline vs placebo, in terms of dryness of the oral cavity
and salivary flow, in patients with xerostomia secondary to radiotherapy for cancers in
the head and neck region.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral cevimeline 3 times daily for 12 weeks in the absence of
PROJECTED ACCRUAL: A total of 280 patients (140 per arm) will be accrued for this study.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
DISEASE CHARACTERISTICS:
- Received more than 4,000 cGy of prior external beam radiotherapy for cancer in the
head and neck region
- Radiotherapy completed more than 4 months prior to study
- Clinically significant salivary gland dysfunction with grade 2 or 3 xerostomia
- At least 1 anatomically intact parotid gland
- No suspected or confirmed bilateral physical closure of salivary gland ducts
- No history of primary or secondary Sjogren's syndrome or other underlying systemic
illness known to cause xerostomia independent of prior radiotherapy exposure
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Karnofsky 70-100%
- ECOG 0-2
Life expectancy:
- At least 6 months
Hematopoietic:
- Hemoglobin at least 9. 0 g/dL
- No anemia
Hepatic:
- Bilirubin no greater than 2 times upper limit of normal (ULN)
- SGOT/SGPT no greater than 2 times ULN
- Lactate dehydrogenase no greater than 2 times ULN
- No evidence of active liver disease
Renal:
- Creatinine no greater than 2. 5 mg/dL
- BUN no greater than 50 mg/dL
- No history of nephrolithiasis within the past 6 months
Cardiovascular:
- No history of significant cardiovascular disease
- No active congestive heart failure
- No uncontrolled angina
- No significant arrhythmia
- No myocardial infarction within the past 6 months
Pulmonary:
- No history of significant pulmonary disease
- No controlled or uncontrolled asthma
- No chronic bronchitis or chronic obstructive pulmonary disease that would limit
avocational activities
Gastrointestinal:
- No history of significant gastrointestinal disorder
- No active pancreatic disease
- No gastroduodenal ulcers within the past 6 months
- No hypersensitive bowel conditions requiring pharmacologic therapy
- No inflammatory bowel disease
- No history of cholelithiasis within the past 6 months (unless cholecystectomy
performed)
Other:
- No clinically significant laboratory abnormality
- No history of alcohol or drug abuse within the past 6 months that would preclude
study
- No prior or concurrent acute iritis or narrow-angle (angle closure) glaucoma
- Not pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- No concurrent chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- See Disease Characteristics
- No concurrent radiotherapy
Surgery:
- Not specified
Other:
- At least 30 days since other investigational new drug
- At least 4 weeks since prior systemic or ophthalmic pilocarpine
- No prior cevimeline
- No concurrent hyperbaric oxygen therapy
- No concurrent beta adrenergic antagonists, anticholinergic agents, cevimeline
metabolism inhibitors, or other medications known to effect salivary function
- No other concurrent investigational drugs
University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama 35294-3300, United States
Mobile Infirmary Medical Center, Mobile, Alabama 36607, United States
Cranial Pain Research, Tucson, Arizona 85711, United States
University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205-7199, United States
Alta Bates Comprehensive Cancer Center, Berkeley, California 94704, United States
Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095-1781, United States
Chao Family Comprehensive Cancer Center, Orange, California 92868, United States
Radiation Oncology Center - Sacramento, Sacramento, California 95816, United States
Rebecca and John Moores UCSD Cancer Center, San Diego, California 92103-8757, United States
Stanford University Medical Center, Stanford, California 94305-5408, United States
Colorado Otolaryngology Associates, Colorado Springs, Colorado 80909, United States
University of Connecticut Health Center, Farmington, Connecticut 06360-7106, United States
Walter Reed Army Medical Center, Washington, District of Columbia 20307-5000, United States
Innovative Medical Research of South Florida, Inc., Miami, Florida 33138, United States
Medical College of Georgia Hospital and Clinics, Augusta, Georgia 30912, United States
Kootenai Medical Center, Coeur d'Alene, Idaho 83814, United States
University of Chicago Cancer Research Center, Chicago, Illinois 60637-1470, United States
University of Illinois at Chicago, Chicago, Illinois 60612-7317, United States
Evanston Northwestern Health Care, Evanston, Illinois 60201, United States
University of Kansas Medical Center, Kansas City, Kansas 66160-7321, United States
Central Baptist Hospital, Lexington, Kentucky 40503, United States
Louisville, Kentucky 40207, United States
James Graham Brown Cancer Center, Louisville, Kentucky 40202-3267, United States
Tulane Cancer Center, New Orleans, Louisiana 70112-2699, United States
Harbor Hospital Center, Baltimore, Maryland 21215-1290, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21287-0910, United States
Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States
Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States
Ear, Nose, and Throat Specialty Care of Minnesota, P.A., Minneapolis, Minnesota 55404, United States
University of Minnesota School of Dentistry, Minneapolis, Minnesota 55455, United States
University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States
University of Missouri, Columbia, Missouri 65212, United States
Siteman Cancer Center, Saint Louis, Missouri 63110-1093, United States
University of Nebraska Medical Center, Lincoln, Nebraska 68583, United States
University of Nebraska Medical Center, Omaha, Nebraska 68198-1225, United States
Norris Cotton Cancer Center, Lebanon, New Hampshire 03756-0002, United States
Hackensack University Medical Center, Hackensack, New Jersey 07601, United States
Monmouth Medical Center, Long Branch, New Jersey 07740-6395, United States
Professional Otolaryngology Associates, Voorhees, New Jersey 08043, United States
Albert Einstein Clinical Cancer Center, Bronx, New York 10461, United States
North Shore University Hospital, Manhasset, New York 11030, United States
Mount Sinai Medical Center, NY, New York, New York 10029, United States
NYU - David B. Kriser Dental Center, New York, New York 10010-4086, United States
James P. Wilmot Cancer Center, Rochester, New York 14642, United States
State University of New York at Stony Brook School of Medicine, Stony Brook, New York 11794-8706, United States
State University of New York - Upstate Medical University, Syracuse, New York 13210, United States
Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States
Comprehensive Cancer Center at Gaston Memorial, Gastonia, North Carolina 28053-1747, United States
Matthews Radiation Oncology Center, Matthews, North Carolina 28105, United States
Clinical Research of Winston Salem, Winston-Salem, North Carolina 27103, United States
Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195, United States
Oregon Cancer Institute, Portland, Oregon 97239, United States
Geisinger Medical Center, Danville, Pennsylvania 17822-1333, United States
Head and Neck Associates, Havertown, Pennsylvania 19083, United States
Associated Otolaryngologist, Palmyra, Pennsylvania 17078, United States
Kimmel Cancer Center of Thomas Jefferson University - Philadelphia, Philadelphia, Pennsylvania 19107-5541, United States
University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania 19104-4283, United States
Eye and Ear Institute, Pittsburgh, Pennsylvania 15213, United States
Medical University of South Carolina, Charleston, South Carolina 29425, United States
Memorial Hospital Cancer Center - Chattanooga, Chattanooga, Tennessee 37404, United States
MultiSpecialty Clinical Research, Johnson City, Tennessee 37601, United States
Dial Research Associates, Inc., Nashville, Tennessee 37205, United States
Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-5671, United States
Baylor College of Dentistry, Dallas, Texas 75246, United States
University of Texas - MD Anderson Cancer Center, Houston, Texas 77030-4009, United States
Cancer Physicians Associates, PA, Laredo, Texas 78041, United States
Latter Day Saints Hospital, Salt Lake City, Utah 84143, United States
McLean, Virginia 22101, United States
Seattle Institute for Biomedical and Clinical Research, Seattle, Washington 98108, United States
Madigan Army Medical Center, Tacoma, Washington 98431, United States
Southwest Washington Medical Center, Vancouver, Washington 98664, United States