title: Phase I trial of daily oral Polyphenon E in patients with asymptomatic Rai stage 0 to II chronic lymphocytic leukemia.
abstract: OBJECTIVE
  To define the optimal dose of Polyphenon E for chronic daily administration and tolerability in patients with chronic lymphocytic leukemia (CLL).
  
  
  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).
  
  
  CONCLUSIONS
  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.affiliation: Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. shanafelt.tait@mayo.edu
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
authors.forename: Tim G
authors.initials: TG
authors.lastname: Call
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.forename: Betsy
authors.initials: B
authors.lastname: LaPlant
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Bowen
authors.forename: Michelle
authors.initials: M
authors.lastname: Roos
authors.forename: Charla R
authors.initials: CR
authors.lastname: Secreto
authors.forename: Asish K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Brian F
authors.initials: BF
authors.lastname: Kabat
authors.forename: Mao-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Chung S
authors.initials: CS
authors.lastname: Yang
authors.forename: Diane F
authors.initials: DF
authors.lastname: Jelinek
authors.forename: Charles
authors.initials: C
authors.lastname: Erlichman
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002392:Catechin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D013662:Tea; D016896:Treatment Outcome
chemical_list: D016588:Anticarcinogenic Agents; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; C472086:polyphenon E