Regression of oral leukoplakia with alpha-tocopherol: a community clinical oncology program chemoprevention study

Abstract

BACKGROUND: Oral leukoplakia is an important model for developing chemoprevention approaches for lesions in the upper aerodigestive tract. These lesions most often result from exposure to carcinogens such as tobacco and alcohol and may precede development of invasive cancer. The potent antioxidant alpha-tocopherol (vitamin E) has prevented the development of cancers of the oral cavities in animal models.

PURPOSE: The objectives of this study were to evaluate the toxicity and efficacy of alpha-tocopherol in patients with oral leukoplakia and to assess the feasibility of performing chemoprevention trials through the network of the Community Clinical Oncology Program (CCOP).

METHODS: A single-arm phase II study using the nontoxic agent alpha-tocopherol to treat oral premalignant leukoplakia was performed at seven institutions affiliated with the CCOP through The University of Texas M. D. Anderson Cancer Center. Patients with symptomatic leukoplakia or dysplasia were treated orally with alpha-tocopherol (400 IU) twice daily for 24 weeks. Follow-up was performed at 6, 12, and 24 weeks after the start of treatment to assess toxicity and response, and serum alpha-tocopherol levels were determined at baseline and at 6 and 24 weeks.

RESULTS: Of the 43 patients who have completed 24 weeks of treatment, 20 (46%) had clinical responses and nine (21%) had histologic responses. Mean serum alpha-tocopherol levels were 16.1 micrograms/mL at baseline and increased to 34.29 micrograms/mL after 24 weeks of treatment. Patient-recorded drug calendars, as well as serum drug levels, indicated excellent patient compliance; an average of 95% of the prescribed pills were taken. Treatment was extremely well tolerated; no grade 3 or 4 toxic effects were reported.

CONCLUSIONS: Administration of alpha-tocopherol resulted in both clinical and histologic responses in premalignant leukoplakia lesions. The study also demonstrated that chemoprevention trials can be performed through the CCOP. The major problems were that a high percentage of patients were not assessable for response, some patients withdrew because expenses were not reimbursable, and there was limited participation within the CCOP network. These problems may reflect difficulties inherent in the implementation of multi-institutional chemoprevention trials.

IMPLICATIONS: The efficacy of alpha-tocopherol alone and in combination with other chemopreventive agents for carcinogenesis in the upper aerodigestive tract should be explored in future trials.

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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E, approximately 20 grams per day orally);

- Cancer and Vitamin E (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives - Approximately 60mg per day orally: 40mg per day Beta-Carotene/β-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate);

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives) - In vitro, review and in vivo publications;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Neuroblastoma: Complete objective response to biological treatment;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma.