Beta-carotene and Alpha-tocopherol Chemoprevention of Second Primary Malignancies in Head and Neck Cancer Patients

Study Overview
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Brief Summary
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Epidemiologic studies suggest that low dietary intakes and low plasma concentrations of antioxidant vitamins and minerals are associated with increased risks of cancer, especially for epidermoid tumors. Patients with stage I or II head and neck cancer have a good prognosis, with a 5-year relative survival of 60% to 90%, depending of the tumor site. However, the benefit of treatment is often compromised by the occurrence of second primary cancers, which develop in 20% of patients during the first 5 years after diagnosis. We conducted a randomized chemoprevention trial among patients with head and neck cancer treated by radiation therapy to determine whether supplementation combining two antioxidants, alpha-tocopherol and beta-carotene, could reduce the incidence of second primary cancers in this patient population (primary objective of the trial). This study was conducted with funds from the NCIC (#008176,004738,013211) and was completed. In this cohort of head and neck cancer patients, we evaluated whether nine potential prognostic serum markers measured at the time of diagnosis were related to recurrence, occurence of second primary cancers and survival. This study was conducted with funds from the NCIC (#018100) and was completed. Presently, we evaluate genetic polymorphisms(GWAS) associated with prognosis (NCIC grant #019502). We also assess the relationship between vitamin D (dietary intake, serum level, and genetic polymorphisms of key vitamin D-related genes) and head and neck long-term outcomes (NCI grant #1R03CA141615-01).

Official Title
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Beta-carotene and Alpha-tocopherol Chemoprevention of Second Primary Malignancies in Head and Neck Cancer Patients

Conditions
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Neoplasms

Intervention / Treatment
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* Dietary Supplement: Alpha-Tocopherol and Beta-Carotene
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented stage I or II head and neck cancer Exclusion Criteria: Karnofsky performance score of less than 60 Multiple primary head and neck cancer History of cancer Severe cardiovascular disease Inadequate renal, hepatic or hematologic function Anticoagulant therapy Pregnancy Average daily supplement intake of beta-carotene or vitamin E in the preceding year greater than 6.0 mg and 50 IU, respectively.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alpha-Tocopherol and Beta-Carotene<br>Patients received a daily supplementation of alpha-tocopherol (one capsule of 400 IU dl-alpha-tocopherol) and beta-carotene (one capsule of 30 mg) for 3 years after the end of radiation therapy. Due to ethical concerns, the beta-carotene supplementation was stopped during the trial (after the randomization of 156 patients). See details in JNCI, 2005: 97 (7), 481-8. | Dietary Supplement: Alpha-Tocopherol and Beta-Carotene<br>* Provided by Roche Vitamins Inc.<br>|
| Placebo Comparator: Placebo<br>Patients received two capsules of placebos per day during 3 years. When the beta-carotene was stopped, they received only one capsule. | Dietary Supplement: Placebo<br>* Provided by Roche Vitamins Inc<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Second primary cancers |  | Immediately and 1 month after radiation therapy, every 6 months during the 3 years following the end of radiation therapy, and then once a year until June 30, 2003 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute and late side-effects of radiation therapy |  | During radiation therapy (RT), at the end of RT, one month after RT, six months after RT and 1 year after RT | 
| Quality of life |  | Baseline, at the end of radiation therapy (RT), 1, 6,12,24 and 36 months after RT | 
| Recurrence |  | Immediately and 1 month after radiation therapy, every 6 months during the 3 years following the end of radiation therapy, and then once a year until June 30, 2003 | 
| Cancer free survival | Without recurrence and without second primary cancer | Immediately and 1 month after radiation therapy, every 6 months during the 3 years following the end of radiation therapy, and then once a year until June 30, 2003 | 
| Overall survival |  | Every year | 
| Disease free survival | Alive and without recurrence | Immediately and 1 month after radiation therapy, every 6 months during the 3 years following the end of radiation therapy, and then once a year until June 30, 2003 | 
| Survival until death from first cancer |  | every year | 
| Survival until death from second primary cancer |  | Every year | 
| Survival until death from non-cancer causes |  | Every year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chemoprevention trial, antioxidant, alpha-tocopherol, beta-carotene, second primary cancer, head and neck cancer, adverse effect of radiation therapy, quality of life, mortality, cancer free survival, cancer recurrence