Phase I trial of daily oral polyphenon E in patients with asymptomatic rai stage 0 to II chronic lymphocytic leukemia

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

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114 Citations (Scopus)

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 ≥ 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.

Original languageEnglish (US)
Pages (from-to)3808-3814
Number of pages7
JournalJournal of Clinical Oncology
Volume27
Issue number23
DOIs
StatePublished - Aug 10 2009

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B-Cell Chronic Lymphocytic Leukemia
National Cancer Institute (U.S.)
Lymphocyte Count
polyphenon E
Maximum Tolerated Dose
Nausea
Abdominal Pain
Mouth
Therapeutics
epigallocatechin gallate

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Shanafelt, T. D., Call, T. G., Zent, C. S., LaPlant, B., Bowen, D. A., Roos, M., ... Kay, N. E. (2009). Phase I trial of daily oral polyphenon E in patients with asymptomatic rai stage 0 to II chronic lymphocytic leukemia. Journal of Clinical Oncology, 27(23), 3808-3814. https://doi.org/10.1200/JCO.2008.21.1284
Shanafelt, Tait D. ; Call, Tim G. ; Zent, Clive S. ; LaPlant, Betsy ; Bowen, Deborah A. ; Roos, Michelle ; Secreto, Charla R. ; Ghosh, Asish K. ; Kabat, Brian F. ; Lee, Mao Jung ; Yang, Chung S. ; Jelinek, Diane F. ; Erlichman, Charles ; Kay, Neil E. / Phase I trial of daily oral polyphenon E in patients with asymptomatic rai stage 0 to II chronic lymphocytic leukemia. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 23. pp. 3808-3814.
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title = "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 ≥ 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.",
author = "Shanafelt, {Tait D.} and Call, {Tim G.} and Zent, {Clive S.} and Betsy LaPlant and Bowen, {Deborah A.} and Michelle Roos and Secreto, {Charla R.} and Ghosh, {Asish K.} and Kabat, {Brian F.} and Lee, {Mao Jung} and Yang, {Chung S.} and Jelinek, {Diane F.} and Charles Erlichman and Kay, {Neil E.}",
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Shanafelt, TD, Call, TG, Zent, CS, LaPlant, B, Bowen, DA, Roos, M, Secreto, CR, Ghosh, AK, Kabat, BF, Lee, MJ, Yang, CS, Jelinek, DF, Erlichman, C & Kay, NE 2009, 'Phase I trial of daily oral polyphenon E in patients with asymptomatic rai stage 0 to II chronic lymphocytic leukemia', Journal of Clinical Oncology, vol. 27, no. 23, pp. 3808-3814. https://doi.org/10.1200/JCO.2008.21.1284

Phase I trial of daily oral polyphenon E in patients with asymptomatic rai stage 0 to II chronic lymphocytic leukemia. / Shanafelt, Tait D.; Call, Tim G.; Zent, Clive S.; LaPlant, Betsy; Bowen, Deborah A.; Roos, Michelle; Secreto, Charla R.; Ghosh, Asish K.; Kabat, Brian F.; Lee, Mao Jung; Yang, Chung S.; Jelinek, Diane F.; Erlichman, Charles; Kay, Neil E.

In: Journal of Clinical Oncology, Vol. 27, No. 23, 10.08.2009, p. 3808-3814.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase I trial of daily oral polyphenon E in patients with asymptomatic rai stage 0 to II chronic lymphocytic leukemia

AU - Shanafelt, Tait D.

AU - Call, Tim G.

AU - Zent, Clive S.

AU - LaPlant, Betsy

AU - Bowen, Deborah A.

AU - Roos, Michelle

AU - Secreto, Charla R.

AU - Ghosh, Asish K.

AU - Kabat, Brian F.

AU - Lee, Mao Jung

AU - Yang, Chung S.

AU - Jelinek, Diane F.

AU - Erlichman, Charles

AU - Kay, Neil E.

PY - 2009/8/10

Y1 - 2009/8/10

N2 - 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.

AB - 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.

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