Phase I Trial of Oral Green Tea Extract in Adult Patients With Solid Tumors

• Published in: Journal of clinical oncology Vol. 19; no. 6; pp. 1830 - 1838
• Main Authors: PISTERS, Katherine M. W, NEWMAN, Robert A, COLDMAN, Brenda, SHIN, Dong M, KHURI, Fadlo R, HONG, Waun Ki, GLISSON, Bonnie S, LEE, Jin S
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 15.03.2001; Lippincott Williams & Wilkins
• Subjects: Administration, Oral; Adult; Aged; Antineoplastic agents; Biological and medical sciences; Caffeine - administration & dosage; Caffeine - adverse effects; Caffeine - pharmacology; Chemotherapy; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - adverse effects; Drugs, Chinese Herbal - pharmacokinetics; Drugs, Chinese Herbal - therapeutic use; Female; Humans; Male; Medical sciences; Middle Aged; Neoplasms - drug therapy; Neoplasms - pathology; Pharmacokinetics; Pharmacology. Drug treatments; Phytotherapy; Tea - adverse effects; Tea - therapeutic use; Antineoplastic agent; Human; Catechin; Pharmacognosy; Maximal dose; Toxicity; Oral administration; Malignant tumor; Chemotherapy; Polyphenol; Treatment; Analog; Plant origin; Phase I trial; Complication; Tea extract; Pharmacokinetics; Green tea
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2001.19.6.1830

This trial was designed to determine the maximum-tolerated dose, toxicity, and pharmacology of oral green tea extract (GTE) once daily or three times daily. Cohorts of three or more adult cancer patients were administered oral GTE with water after meals one or three times daily for 4 weeks, to a maximum of 6 months, depending on disease response and patient tolerance. Pharmacokinetic analyses were encouraged but optional. Dose levels of 0.5 to 5.05 g/m(2) qd and 1.0 to 2.2 g/m(2) tid were explored. A total of 49 patients were studied. median age, 57 years (range, 27 to 77 years); 23 patients were women (47%); 98% had a Zubrod PS of 1%; 98% had PS of 1; and 21 had non-small-cell lung, 19 had head & neck cancer, three had mesothelioma, and six had other. Mild to moderate toxicities were seen at most dose levels and promptly reversed on discontinuation of GTE. Dose-limiting toxicities were caffeine related and included neurologic and gastrointestinal effects. The maximum-tolerated dose was 4.2 g/m(2) once daily or 1.0 g/m(2) three times daily. No major responses occurred; 10 patients with stable disease completed 6 months of GTE. Pharmacokinetic analyses found accumulation of caffeine levels that were dose dependent, whereas epigallocatechin gallate levels did not accumulate nor appear dose related. A dose of 1.0 g/m(2) tid (equivalent to 7 to 8 Japanese cups [120 mL] of green tea three times daily) is recommended for future studies. The side effects of this preparation of GTE were caffeine related. Oral GTE at the doses studied can be taken safely for at least 6 months.