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

Tait D. Shanafelt, Timothy G. Call, Clive S. Zent, Jose F. Leis, Betsy Laplant, Deborah A. Bowen, Michelle Roos, Kristina Laumann, Asish K. Ghosh, Connie Lesnick, Mao Jung Lee, Chung S. Yang, Diane F Jelinek, Charles Erlichman, Neil Elliot Kay

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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 × 109/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.

Original languageEnglish (US)
Pages (from-to)363-370
Number of pages8
JournalCancer
Volume119
Issue number2
DOIs
StatePublished - Jan 15 2013

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B-Cell Chronic Lymphocytic Leukemia
Lymphocyte Count
Lymph Nodes
National Cancer Institute (U.S.)
Tea
Terminology
Fatigue
Therapeutics

Keywords

  • chronic lymphocytic leukemia
  • early stage
  • green tea
  • prognosis
  • treatment

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase 2 trial of daily, oral polyphenon e in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia. / Shanafelt, Tait D.; Call, Timothy G.; Zent, Clive S.; Leis, Jose F.; Laplant, Betsy; Bowen, Deborah A.; Roos, Michelle; Laumann, Kristina; Ghosh, Asish K.; Lesnick, Connie; Lee, Mao Jung; Yang, Chung S.; Jelinek, Diane F; Erlichman, Charles; Kay, Neil Elliot.

In: Cancer, Vol. 119, No. 2, 15.01.2013, p. 363-370.

Research output: Contribution to journalArticle

Shanafelt, TD, Call, TG, Zent, CS, Leis, JF, Laplant, B, Bowen, DA, Roos, M, Laumann, K, Ghosh, AK, Lesnick, C, Lee, MJ, Yang, CS, Jelinek, DF, Erlichman, C & Kay, NE 2013, 'Phase 2 trial of daily, oral polyphenon e in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia', Cancer, vol. 119, no. 2, pp. 363-370. https://doi.org/10.1002/cncr.27719
Shanafelt, Tait D. ; Call, Timothy G. ; Zent, Clive S. ; Leis, Jose F. ; Laplant, Betsy ; Bowen, Deborah A. ; Roos, Michelle ; Laumann, Kristina ; Ghosh, Asish K. ; Lesnick, Connie ; Lee, Mao Jung ; Yang, Chung S. ; Jelinek, Diane F ; Erlichman, Charles ; Kay, Neil Elliot. / Phase 2 trial of daily, oral polyphenon e in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia. In: Cancer. 2013 ; Vol. 119, No. 2. pp. 363-370.
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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 × 109/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.",
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T1 - Phase 2 trial of daily, oral polyphenon e in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia

AU - Shanafelt, Tait D.

AU - Call, Timothy G.

AU - Zent, Clive S.

AU - Leis, Jose F.

AU - Laplant, Betsy

AU - Bowen, Deborah A.

AU - Roos, Michelle

AU - Laumann, Kristina

AU - Ghosh, Asish K.

AU - Lesnick, Connie

AU - Lee, Mao Jung

AU - Yang, Chung S.

AU - Jelinek, Diane F

AU - Erlichman, Charles

AU - Kay, Neil Elliot

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N2 - 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 × 109/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.

AB - 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 × 109/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.

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