Benner S E, Winn R J, Lippman S M, Poland J, Hansen K S, Luna M A, Hong W K
Department of Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
J Natl Cancer Inst. 1993 Jan 6;85(1):44-7. doi: 10.1093/jnci/85.1.44.
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.
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).
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.
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.
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.
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.
口腔白斑是开发上消化道病变化学预防方法的重要模型。这些病变大多是由于接触烟草和酒精等致癌物引起的，可能先于浸润性癌的发生。强效抗氧化剂α-生育酚（维生素E）已在动物模型中预防了口腔癌的发生。
本研究的目的是评估α-生育酚对口腔白斑患者的毒性和疗效，并通过社区临床肿瘤项目（CCOP）网络评估进行化学预防试验的可行性。
通过德克萨斯大学MD安德森癌症中心，在CCOP下属的7家机构进行了一项单臂II期研究，使用无毒药物α-生育酚治疗口腔癌前白斑。有症状的白斑或发育异常患者口服α-生育酚（400 IU），每日2次，共24周。在治疗开始后的6周、12周和24周进行随访，以评估毒性和反应，并在基线以及6周和24周时测定血清α-生育酚水平。
在完成24周治疗的43例患者中，20例（46%）有临床反应，9例（21%）有组织学反应。基线时血清α-生育酚平均水平为16.1微克/毫升，治疗24周后升至34.29微克/毫升。患者记录的用药日历以及血清药物水平表明患者依从性良好；平均服用了95%的处方药物。治疗耐受性极佳；未报告3级或4级毒性反应。
给予α-生育酚可使癌前白斑病变出现临床和组织学反应。该研究还表明可以通过CCOP进行化学预防试验。主要问题是有很大比例的患者无法评估反应，一些患者因费用无法报销而退出，且CCOP网络内参与度有限。这些问题可能反映了多机构化学预防试验实施中固有的困难。
未来试验应探索单独使用α-生育酚以及与其他化学预防剂联合对上消化道致癌作用的疗效。
