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.

Conflict of interest statement

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

Figures

Fig 1.

Plasma levels of epigallocatechin-3-gallate (EGCG) and response. Figure shows the relationship between absolute lymphocyte count (ALC) reduction at 1 month (x-axis) and trough plasma EGCG level (y-axis) at 1 month. EGCG plasma levels are shown on a log normal scale as a result of the wide variation in plasma levels.