Phase I trial of daily oral Polyphenon E in patients with asymptomatic Rai stage 0 to II chronic lymphocytic leukemia.

Abstract

PURPOSE:

To define the optimal dose of Polyphenon E for chronic daily administration and tolerability in patients with chronic lymphocytic leukemia (CLL).

PATIENTS AND METHODS:

Previously untreated patients with asymptomatic Rai stage 0 to II CLL were eligible for participation. Polyphenon E with a standardized dose of epigallocatechin-3-gallate (EGCG) was administered using the standard phase I design with three to six patients per dose level (range, 400 to 2,000 mg by mouth twice a day). Trough plasma EGCG levels were measured 1 month after initiation of therapy. Response was classified using the National Cancer Institute (NCI) Working Group (WG) Criteria.

RESULTS:

Thirty-three eligible patients were accrued to dose levels 1 to 8. The maximum-tolerated dose was not reached. The most common adverse effects included transaminitis (33%, all grade 1), abdominal pain (30% grade 1, 0% grade 2, and 3% grade 3), and nausea (39% grade 1 and 9% grade 2). One patient experienced an NCI WG partial remission. Other signs of clinical activity were also observed, with 11 patients (33%) having a sustained > or = 20% reduction in absolute lymphocyte count (ALC) and 11 (92%) of 12 patients with palpable adenopathy experiencing at least a 50% reduction in the sum of the products of all nodal areas during treatment. Trough plasma EGCG levels after 1 month of treatment ranged from 2.9 to 3,974 ng/mL (median, 40.4 ng/mL).

CONCLUSION:

Daily oral EGCG in the Polyphenon E preparation was well tolerated by CLL patients in this phase I trial. Declines in ALC and/or lymphadenopathy were observed in the majority of patients. A phase II trial to evaluate efficacy using 2,000 mg twice a day began in November 2007.

• Authors: Tait D Shanafelt, Tim G Call, Clive S Zent, Betsy LaPlant, Deborah A Bowen, Michelle Roos, Charla R Secreto, Asish K Ghosh, Brian F Kabat, Mao-Jung Lee, Chung S Yang, Diane F Jelinek, Charles Erlichman, Neil E Kay
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 23 Pg. 3808-14 (Aug 10 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19470922 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Tea
• Catechin
• epigallocatechin gallate
• polyphenon E

Topics

• Administration, Oral
• Adult
• Aged
• Anticarcinogenic Agents (administration & dosage, adverse effects, blood, therapeutic use)
• Catechin (administration & dosage, adverse effects, analogs & derivatives, blood, therapeutic use)
• Female
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Patient Selection
• Tea
• Treatment Outcome