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

Laval University

Status and phase: Completed; Phase 3

Conditions: Neoplasms

Treatments: Dietary Supplement: Placebo; Dietary Supplement: Alpha-Tocopherol and Beta-Carotene

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT00169845

27370

1R03CA141615-01 (U.S. NIH Grant/Contract)

NCIC-4738 (Other Grant/Funding Number)

NCIC-8176 (Other Grant/Funding Number)

NCIC-019502 (Other Grant/Funding Number)

018100 (Other Grant/Funding Number)

NCIC-13211 (Other Grant/Funding Number)

Details and patient eligibility

About

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).

Enrollment: 540 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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540 participants in 2 patient groups, including a placebo group

Alpha-Tocopherol and Beta-Carotene

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Alpha-Tocopherol and Beta-Carotene

Placebo

Placebo Comparator group

Description:

Patients received two capsules of placebos per day during 3 years. When the beta-carotene was stopped, they received only one capsule.

Treatment:

Dietary Supplement: Placebo