Phase 2 trial of daily, oral Polyphenon E in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia

Abstract

Background: The objective of the current study was to follow up the results of phase 1 testing by evaluating the clinical efficacy of the green tea extract Polyphenon E for patients with early stage chronic lymphocytic leukemia (CLL).

Methods: Previously untreated patients with asymptomatic, Rai stage 0 to II CLL and an absolute lymphocyte count (ALC) ≥ 10 × 10(9) /L were eligible for this phase 2 trial. Polyphenon E with a standardized dose of epigallocatechin gallate (EGCG) (2000 mg per dose) was administered twice daily.

Results: A total of 42 patients received Polyphenon E at a dose of 2000 mg twice daily for up to 6 months. Of these patients, 29 (69%) had Rai stage I to II disease. Patients received a median of 6 cycles of treatment (range, 1 cycle-6 cycles). The most common grade 3 side effects (according to National Cancer Institute Common Terminology Criteria for Adverse Events) were transaminitis (1 patient), abdominal pain (1 patient), and fatigue (1 patient). Clinical activity was observed, with 13 patients (31%) experiencing a sustained reduction of ≥ 20% in the ALC and 20 of 29 patients (69%) with palpable adenopathy experiencing at least a 50% reduction in the sum of the products of all lymph node areas. EGCG plasma levels after 1 month of therapy were found to be correlated with reductions in lymphadenopathy (correlation co-efficient, 0.44; P = .02). Overall, 29 patients (69%) fulfilled the criteria for a biologic response with either a sustained decline ≥ 20% in the ALC and/or a reduction ≥ 30% in the sum of the products of all lymph node areas at some point during the 6 months of active treatment.

Conclusions: Daily oral EGCG in the Polyphenon E preparation was well tolerated by patients with CLL in this phase 2 trial. Durable declines in the ALC and/or lymphadenopathy were observed in the majority of patients.

Copyright © 2012 American Cancer Society.

Figures

Figure 1

Absolute lymphocyte counts (ALC) in Patients Discontinuing Therapy because of Increased Serum Transaminase Levels. Time 0 indicates the ALC prior to initiating EGCG therapy. Red arrows indicate the ALC at the time EGCG was discontinued due to the increase in serum transaminase levels.

Figure 2

Reductions in ALC and Lymphadenopathy A: Waterfall plot of best ALC declines during treatment B: Waterfall plot of best reduction in sum of lymph nodes

Figure 3

Treatment Free Survival from Date of Registration A: Treatment Free Survival All Patients from the Date of Registration: Time in months is shown on the x axis. The event free survival is shown on the y axis (initiation of CLL treatment or death were considered events). No deaths have been observed to date; 8 patients required treatment for progressive CLL. B.Treatment Free Survival from Date of Registration by ZAP-70 Status: The event free survival of ZAP-70 positive (n=12) and ZAP-70 negative (n=30) patients are shown (Log rank p-value: 0.53).

Figure 3

Treatment Free Survival from Date of Registration A: Treatment Free Survival All Patients from the Date of Registration: Time in months is shown on the x axis. The event free survival is shown on the y axis (initiation of CLL treatment or death were considered events). No deaths have been observed to date; 8 patients required treatment for progressive CLL. B.Treatment Free Survival from Date of Registration by ZAP-70 Status: The event free survival of ZAP-70 positive (n=12) and ZAP-70 negative (n=30) patients are shown (Log rank p-value: 0.53).