RATIONALE: Drugs used in chemotherapy such as isotretinoin use different ways to stop tumor
cells from dividing so they stop growing or die. Interferon alfa may interfere with the
growth of tumor cells. Vitamin E may be able to decrease side effects caused by
isotretinoin. It is not yet known whether combining isotretinoin and interferon alfa with
vitamin E is more effective than observation in preventing recurrence of head and neck
cancer after surgery and/or radiation therapy.
PURPOSE: Randomized phase III trial to compare the effectiveness of isotretinoin and
interferon alfa combined with vitamin E with that of observation in treating patients who
have undergone surgery and/or radiation therapy for stage III or stage IV head and neck
cancer.
- Determine the efficacy of adjuvant isotretinoin, interferon alfa, and vitamin E, in
terms of incidence of primary disease recurrence and secondary primary tumor
development, in patients with stage III or IV squamous cell carcinoma of the head and
neck previously treated with definitive surgical excision and/or postoperative
radiotherapy.
- Determine the qualitative and quantitative toxicity of this regimen in these patients.
- Compare the overall and disease-free survival of patients treated with this regimen vs
- Determine whether alterations of p53 gene, retinoic acid receptors, retinoid-regulated
gene, and interferon-responsive genes are associated with clinical outcome in these
patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to T
stage (T1 or T2 vs T3 or T4), N stage (N0 or N1 vs N2 or N3), prior therapy (complete tumor
resection vs resection and radiotherapy/chemoradiotherapy vs radiotherapy or
chemoradiotherapy alone), and prior chemotherapy (yes vs no). Patients are randomized to 1
of 2 treatment arms.
- Arm I: Patients receive oral isotretinoin once daily, interferon alfa subcutaneously 3
times weekly, and oral vitamin E 3 times daily. Treatment repeats every month for 12
courses (1 year) in the absence of disease recurrence or unacceptable toxicity.
- Arm II: Patients undergo observation only for 1 year. Patients are followed every 3
months for 2 years and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 376 patients (188 per treatment arm) will be accrued for this
study within 3. 75 years.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
DISEASE CHARACTERISTICS:
- Histologically confirmed squamous cell carcinoma of the head and neck
- Primary site must be within the oral cavity, oropharynx, larynx, or hypopharynx
- Stage III or IV primary lesion at diagnosis
- No distant metastatic disease at diagnosis
- No multiple primary lesions
- Currently disease-free after treatment with 1 of the following:
- Complete tumor resection
- Radiotherapy or chemoradiotherapy alone*
- Resection followed by radiotherapy/chemoradiotherapy*
- No more than 4-16 weeks since prior surgery and/or radiotherapy/chemoradiotherapy
NOTE: *Radiotherapy must have been 70-72 Gy in 1. 8-2. 0 Gy fractions to the primary
tumor and clinically positive neck nodes and 44-50 Gy in 1. 8-2. 0 Gy fractions to
clinically negative nodes, including the lower neck
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic
- Bilirubin no greater than 1. 5 mg/dL
- AST and ALT no greater than 2 times upper limit of normal (ULN)
- Alkaline phosphatase no greater than 2 times ULN
Renal
- Creatinine no greater than 1. 2 mg/dL
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception for 1 month prior to, during, and
for 1 month after study therapy
- Electrolytes normal
- Fasting serum triglyceride level no greater than 2 times ULN (anti-triglyceride
medication allowed)
- No other malignancy within the past 2 years except localized basal cell or squamous
cell skin cancer
- No other concurrent medical condition that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy and recovered
- Prior neoadjuvant chemotherapy allowed
- Prior chemotherapy administered concurrently with radiotherapy allowed
- No other concurrent chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- See Disease Characteristics
- Recovered from prior radiotherapy
Surgery
- See Disease Characteristics
- Recovered from prior surgery
Other
- No history of megadose vitamin A (more than 25,000 I. U.)
- No other clinical trial enrollment that would preclude adjuvant systemic therapy
- No concurrent vitamin supplements containing vitamin A
Instituto de Enfermedades Neoplasicas, Lima 34, Peru
MBCCOP - San Juan, San Juan 00921-3201, Puerto Rico
San Juan City Hospital, San Juan 00936-7344, Puerto Rico
Veterans Affairs Medical Center - San Juan, San Juan 00927-5800, Puerto Rico
Pretoria Academic Hospital, Pretoria 0001, South Africa
University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama 35294-3300, United States
CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale, Arizona 85259-5404, United States
City of Hope Comprehensive Cancer Center, Duarte, California 91010-3000, United States
Veterans Affairs Medical Center - Palo Alto, Palo Alto, California 94304-1290, United States
Stanford Cancer Center at Stanford University Medical Center, Stanford, California 94305-5216, United States
CCOP - Christiana Care Health Services, Newark, Delaware 19713, United States
MBCCOP - Howard University Cancer Center, Washington, District of Columbia 20060, United States
Veterans Affairs Medical Center - Gainesville, Gainesville, Florida 32608-1197, United States
Veterans Affairs Medical Center - Miami, Miami, Florida 33125, United States
H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612-9497, United States
Veterans Affairs Medical Center - Tampa (Haley), Tampa, Florida 33612, United States
Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, United States
Veterans Affairs Medical Center - Atlanta (Decatur), Decatur, Georgia 30033, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago, Illinois 60611, United States
Veterans Affairs Medical Center - Lakeside Chicago, Chicago, Illinois 60611-4494, United States
CCOP - Central Illinois, Decatur, Illinois 62526, United States
Decatur Memorial Hospital Cancer Care Institute, Decatur, Illinois 62526, United States
CCOP - Evanston, Evanston, Illinois 60201, United States
CCOP - Illinois Oncology Research Association, Peoria, Illinois 61615-7828, United States
CCOP - Carle Cancer Center, Urbana, Illinois 61801, United States
Indiana University Cancer Center, Indianapolis, Indiana 46202-5289, United States
Veterans Affairs Medical Center - Indianapolis (Roudebush), Indianapolis, Indiana 46202, United States
CCOP - Northern Indiana CR Consortium, South Bend, Indiana 46601, United States
CCOP - Cedar Rapids Oncology Project, Cedar Rapids, Iowa 52403-1206, United States
CCOP - Iowa Oncology Research Association, Des Moines, Iowa 50309-1016, United States
John Stoddard Cancer Center at Iowa Lutheran Hospital, Des Moines, Iowa 50316-2301, United States
John Stoddard Cancer Center at Iowa Methodist Medical Center, Des Moines, Iowa 50309, United States
Mercy Cancer Center at Mercy Medical Center - Des Moines, Des Moines, Iowa 50314, United States
Burgess Health Center, Onawa, Iowa 51040, United States
CCOP - Wichita, Wichita, Kansas 67214-3882, United States
Veterans Affairs Medical Center - Wichita, Wichita, Kansas 67218, United States
CCOP - Ochsner, New Orleans, Louisiana 70121, United States
MBCCOP - LSU Health Sciences Center, New Orleans, Louisiana 70112, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, United States
Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States
Tufts - New England Medical Center, Boston, Massachusetts 02111, United States
CCOP - Michigan Cancer Research Consortium, Ann Arbor, Michigan 48106, United States
CCOP - Kalamazoo, Kalamazoo, Michigan 49007-3731, United States
West Michigan Cancer Center, Kalamazoo, Michigan 49007, United States
CCOP - Duluth, Duluth, Minnesota 55805, United States
University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, United States
Veterans Affairs Medical Center - Minneapolis, Minneapolis, Minnesota 55417-2399, United States
Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States
CCOP - Metro-Minnesota, Saint Louis Park, Minnesota 55416, United States
CCOP - Missouri Valley Cancer Consortium, Omaha, Nebraska 68106, United States
Veterans Affairs Medical Center - Omaha, Omaha, Nebraska 68105, United States
Midlands Cancer Center at Midlands Community Hospital, Papillion, Nebraska 68128-4157, United States
CCOP - Southern Nevada Cancer Research Foundation, Las Vegas, Nevada 89106, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756-0002, United States
Veterans Affairs Medical Center - East Orange, East Orange, New Jersey 07018, United States
CCOP - Northern New Jersey, Hackensack, New Jersey 07601, United States
Cancer Institute of New Jersey at Robert Wood Johnson University Hospital, New Brunswick, New Jersey 08903, United States
MBCCOP - University of New Mexico HSC, Albuquerque, New Mexico 87131, United States
Westmead Breast Centre at NSW Breast Cancer Institute, Westmead, New South Wales 2145, Australia
Westmead Hospital, Westmead, New South Wales 2145, Australia
Albert Einstein Clinical Cancer Center, Bronx, New York 10461, United States
MBCCOP-Our Lady of Mercy Cancer Center, Bronx, New York 10466, United States
Veterans Affairs Medical Center - Brooklyn, Brooklyn, New York 11209, United States
NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York, New York 10016, United States
Veterans Affairs Medical Center - New York, New York, New York 10010, United States
CCOP - Merit Care Hospital, Fargo, North Dakota 58122, United States
Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195, United States
MetroHealth's Cancer Care Center at MetroHealth Medical Center, Cleveland, Ohio 44109, United States
CCOP - Columbus, Columbus, Ohio 43206, United States
CCOP - Toledo Community Hospital, Toledo, Ohio 43623-3456, United States
CCOP - Oklahoma, Tulsa, Oklahoma 74136, United States
CCOP - Geisinger Clinic and Medical Center, Danville, Pennsylvania 17822-2001, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, United States
Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111-2497, United States
Hahnemann University Hospital, Philadelphia, Pennsylvania 19102-1192, United States
Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15236, United States
Veterans Affairs Medical Center - Pittsburgh, Pittsburgh, Pennsylvania 15240, United States
CCOP - MainLine Health, Wynnewood, Pennsylvania 19096, United States
CCOP - Sioux Community Cancer Consortium, Sioux Falls, South Dakota 57104, United States
Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville, Tennessee 37232-6307, United States
Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus, Nashville, Tennessee 37212-2637, United States
CCOP - Scott and White Hospital, Temple, Texas 76508, United States
CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay, Wisconsin 54307-3453, United States
University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792-0001, United States
Veterans Affairs Medical Center - Madison, Madison, Wisconsin 53705, United States
CCOP - Marshfield Clinic Research Foundation, Marshfield, Wisconsin 54449, United States
Medical College of Wisconsin Cancer Center, Milwaukee, Wisconsin 53226-3596, United States
Veterans Affairs Medical Center - Milwaukee (Zablocki), Milwaukee, Wisconsin 53295, United States