Originally published as JCO Early Release 10.1200/JCO.2008.21.1284 on May 26 2009

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Google Scholar Articles by Shanafelt, T. D. Articles by Kay, N. E. PubMed PubMed Citation Articles by Shanafelt, T. D. Articles by Kay, N. E. Social Bookmarking                            What's this?

Phase I Trial of Daily Oral Polyphenon E in Patients With Asymptomatic Rai Stage 0 to II Chronic Lymphocytic Leukemia

From the Department of Internal Medicine, Division of Hematology; Division of Biostatistics, and Departments of Immunology and Oncology, Mayo Clinical, Rochester, MN; and the Department of Chemical Biology, and the Ernest Mario School of Pharmacy Rutgers, the State University of New Jersey, Piscataway, NJ.

Corresponding author: Tait D. Shanafelt, MD, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; e-mail: shanafelt.tait{at}mayo.edu.

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 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.

Supported by grants from the National Cancer Institute (Grants No. CA113408 and CA6912), the CLL Global Research Foundation, CLL Topics, Commonwealth Foundation for Cancer Research, Polyphenon E International, and the Mayo Clinic Cancer Center.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00262743 [ClinicalTrials.gov] .

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?