Administration of a phorbol ester to patients with hematological malignancies: Preliminary results from a phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate

Roger Strair, Dale Schaar, Lauri Goodell, Joseph Aisner, Khew Voon Chin, Joseph Eid, Rachelle Senzon, Xiao Xing Cui, Zheng Tao Han, Beth Knox, Arnold Rabson, Richard Chang, Allan Conney

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Purpose: Phorbol esters are capable of inducing a broad range of cellular effects, including the maturation/differentiation of hematopoietic cell lines (E. Huberman and M. F. Callaham, Proc. Natl. Acad. Sci. USA, 76: 1293-1297, 1979; J. Lotem and L. Sachs, Proc. Natl. Acad. Sci. USA, 76: 5158-5162, 1979; G. Rovera et al., Proc. Natl. Acad. Sci. USA, 76: 2779-2783, 1979; H. P. Koeffler, J. Clin. Investig., 66: 1101-1108, 1980). The ability to induce this differentiation at very low concentrations stimulated investigators to administer a phorbol ester, 12-O-tetradecanoylphorbol-13- acetate (TPA), to patients with myeloid leukemias in the People's Republic of China (Z. T. Han et al., Proc. Natl. Acad. Sci. USA, 95: 5357-5361, 1998). The tolerability of this therapy in China prompted Phase I studies of TPA in the United States. The purpose of this report is to demonstrate the tolerance of TPA at doses that result in detectable biological activity in blood and malignant cells. Experimental Design: TPA was administered to patients with relapsed/refractory hematological malignancies. Results: Phenotypic effects were detected in malignant cells and TPA-associated biological activity was present in blood for up to several hours after the infusion. Conclusions: These studies confirm the feasibility of TPA administration to humans and establish the foundation for the development of phorbol esters as therapy for patients with a variety of malignant and nonmalignant disorders.

Original languageEnglish (US)
Pages (from-to)2512-2518
Number of pages7
JournalClinical Cancer Research
Volume8
Issue number8
StatePublished - Jan 1 2002

Fingerprint

Clinical Trials, Phase I
Phorbol Esters
Tetradecanoylphorbol Acetate
Hematologic Neoplasms
China
Myeloid Leukemia
Feasibility Studies
Blood Cells
Research Design
Research Personnel
Cell Line
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Strair, Roger ; Schaar, Dale ; Goodell, Lauri ; Aisner, Joseph ; Chin, Khew Voon ; Eid, Joseph ; Senzon, Rachelle ; Cui, Xiao Xing ; Han, Zheng Tao ; Knox, Beth ; Rabson, Arnold ; Chang, Richard ; Conney, Allan. / Administration of a phorbol ester to patients with hematological malignancies : Preliminary results from a phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate. In: Clinical Cancer Research. 2002 ; Vol. 8, No. 8. pp. 2512-2518.
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abstract = "Purpose: Phorbol esters are capable of inducing a broad range of cellular effects, including the maturation/differentiation of hematopoietic cell lines (E. Huberman and M. F. Callaham, Proc. Natl. Acad. Sci. USA, 76: 1293-1297, 1979; J. Lotem and L. Sachs, Proc. Natl. Acad. Sci. USA, 76: 5158-5162, 1979; G. Rovera et al., Proc. Natl. Acad. Sci. USA, 76: 2779-2783, 1979; H. P. Koeffler, J. Clin. Investig., 66: 1101-1108, 1980). The ability to induce this differentiation at very low concentrations stimulated investigators to administer a phorbol ester, 12-O-tetradecanoylphorbol-13- acetate (TPA), to patients with myeloid leukemias in the People's Republic of China (Z. T. Han et al., Proc. Natl. Acad. Sci. USA, 95: 5357-5361, 1998). The tolerability of this therapy in China prompted Phase I studies of TPA in the United States. The purpose of this report is to demonstrate the tolerance of TPA at doses that result in detectable biological activity in blood and malignant cells. Experimental Design: TPA was administered to patients with relapsed/refractory hematological malignancies. Results: Phenotypic effects were detected in malignant cells and TPA-associated biological activity was present in blood for up to several hours after the infusion. Conclusions: These studies confirm the feasibility of TPA administration to humans and establish the foundation for the development of phorbol esters as therapy for patients with a variety of malignant and nonmalignant disorders.",
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Administration of a phorbol ester to patients with hematological malignancies : Preliminary results from a phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate. / Strair, Roger; Schaar, Dale; Goodell, Lauri; Aisner, Joseph; Chin, Khew Voon; Eid, Joseph; Senzon, Rachelle; Cui, Xiao Xing; Han, Zheng Tao; Knox, Beth; Rabson, Arnold; Chang, Richard; Conney, Allan.

In: Clinical Cancer Research, Vol. 8, No. 8, 01.01.2002, p. 2512-2518.

Research output: Contribution to journalArticle

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T1 - Administration of a phorbol ester to patients with hematological malignancies

T2 - Preliminary results from a phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate

AU - Strair, Roger

AU - Schaar, Dale

AU - Goodell, Lauri

AU - Aisner, Joseph

AU - Chin, Khew Voon

AU - Eid, Joseph

AU - Senzon, Rachelle

AU - Cui, Xiao Xing

AU - Han, Zheng Tao

AU - Knox, Beth

AU - Rabson, Arnold

AU - Chang, Richard

AU - Conney, Allan

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N2 - Purpose: Phorbol esters are capable of inducing a broad range of cellular effects, including the maturation/differentiation of hematopoietic cell lines (E. Huberman and M. F. Callaham, Proc. Natl. Acad. Sci. USA, 76: 1293-1297, 1979; J. Lotem and L. Sachs, Proc. Natl. Acad. Sci. USA, 76: 5158-5162, 1979; G. Rovera et al., Proc. Natl. Acad. Sci. USA, 76: 2779-2783, 1979; H. P. Koeffler, J. Clin. Investig., 66: 1101-1108, 1980). The ability to induce this differentiation at very low concentrations stimulated investigators to administer a phorbol ester, 12-O-tetradecanoylphorbol-13- acetate (TPA), to patients with myeloid leukemias in the People's Republic of China (Z. T. Han et al., Proc. Natl. Acad. Sci. USA, 95: 5357-5361, 1998). The tolerability of this therapy in China prompted Phase I studies of TPA in the United States. The purpose of this report is to demonstrate the tolerance of TPA at doses that result in detectable biological activity in blood and malignant cells. Experimental Design: TPA was administered to patients with relapsed/refractory hematological malignancies. Results: Phenotypic effects were detected in malignant cells and TPA-associated biological activity was present in blood for up to several hours after the infusion. Conclusions: These studies confirm the feasibility of TPA administration to humans and establish the foundation for the development of phorbol esters as therapy for patients with a variety of malignant and nonmalignant disorders.

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