Phase I trial of infusional cyclophosphamide, doxorubicin, and etoposide plus Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in non-Hodgkin's lymphoma

Joseph A. Sparano, Abdissa Negassa, Erick Lansigan, Robin Locke, Chamath R. De Silva, Peter H. Wiernik

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Purpose: To determine the recommended phase II dose (RPTD) of a 96-h continuous intravenous infusion (CIVI) of cyclophosphamide (200, 300, or 400 mg/m2/d) and etoposide (60 or 90 mg/m2/d) when used in conjunction with doxorubicin (12.5 mg/m2/d) (CDE) given every 28 d plus granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with poor prognosis non-Hodgkin's lymphoma (Group A), and the same regimen given every 21 d (Group B). Methods: In Group A, infusional CDE was repeated every 28 d, GM-CSF (250 μg/m2) was given subcutaneously from d 6 until neutrophil recovery, with dose escalation in cohorts of three to six evaluable patients. The RPTD of cyclophosphamide and etoposide established in Group A was then used with CDE given every 3 wk (Group B) with GM-CSF given on d 6-20, and dose escalation was attempted again. Results: In Group A, the RPTD of cyclophosphamide and etoposide were 300 mg/m2/d and 90 mg/m 2/d, respectively; prolonged neutropenia was the dose-limiting toxicity. In Group B, use of GM-CSF on d 6-20 did not facilitate dose escalation above the RPTD established in Group A. Complete response occurred in 13/26 patients (50%) with no prior chemotherapy, and in 4/16 patients (25%) who had relapsed after prior chemotherapy. Conclusions: Because of the increase in dose and dose-density afforded by the administration of GM-CSF, the relative dose intensity was increased by twofold for cyclophosphamide (400 vs 200 mg/m 2/wk) and etoposide (120 vs 60 mg/m2/wk), and by 1.3-fold for doxorubicin (16.7 vs 12.5 mg/m2/wk).

Original languageEnglish (US)
Pages (from-to)257-267
Number of pages11
JournalMedical Oncology
Volume22
Issue number3
DOIs
StatePublished - Sep 2005

Fingerprint

Etoposide
Granulocyte-Macrophage Colony-Stimulating Factor
Non-Hodgkin's Lymphoma
Doxorubicin
Cyclophosphamide
Drug Therapy
Neutropenia
Intravenous Infusions
Neutrophils

Keywords

  • Granulocyte-macrophage colony stimulating factor
  • Non-Hodgkin's lymphoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase I trial of infusional cyclophosphamide, doxorubicin, and etoposide plus Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in non-Hodgkin's lymphoma. / Sparano, Joseph A.; Negassa, Abdissa; Lansigan, Erick; Locke, Robin; De Silva, Chamath R.; Wiernik, Peter H.

In: Medical Oncology, Vol. 22, No. 3, 09.2005, p. 257-267.

Research output: Contribution to journalArticle

@article{137ef3f2d4ae43658dba0386055b59c9,
title = "Phase I trial of infusional cyclophosphamide, doxorubicin, and etoposide plus Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in non-Hodgkin's lymphoma",
abstract = "Purpose: To determine the recommended phase II dose (RPTD) of a 96-h continuous intravenous infusion (CIVI) of cyclophosphamide (200, 300, or 400 mg/m2/d) and etoposide (60 or 90 mg/m2/d) when used in conjunction with doxorubicin (12.5 mg/m2/d) (CDE) given every 28 d plus granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with poor prognosis non-Hodgkin's lymphoma (Group A), and the same regimen given every 21 d (Group B). Methods: In Group A, infusional CDE was repeated every 28 d, GM-CSF (250 μg/m2) was given subcutaneously from d 6 until neutrophil recovery, with dose escalation in cohorts of three to six evaluable patients. The RPTD of cyclophosphamide and etoposide established in Group A was then used with CDE given every 3 wk (Group B) with GM-CSF given on d 6-20, and dose escalation was attempted again. Results: In Group A, the RPTD of cyclophosphamide and etoposide were 300 mg/m2/d and 90 mg/m 2/d, respectively; prolonged neutropenia was the dose-limiting toxicity. In Group B, use of GM-CSF on d 6-20 did not facilitate dose escalation above the RPTD established in Group A. Complete response occurred in 13/26 patients (50{\%}) with no prior chemotherapy, and in 4/16 patients (25{\%}) who had relapsed after prior chemotherapy. Conclusions: Because of the increase in dose and dose-density afforded by the administration of GM-CSF, the relative dose intensity was increased by twofold for cyclophosphamide (400 vs 200 mg/m 2/wk) and etoposide (120 vs 60 mg/m2/wk), and by 1.3-fold for doxorubicin (16.7 vs 12.5 mg/m2/wk).",
keywords = "Granulocyte-macrophage colony stimulating factor, Non-Hodgkin's lymphoma",
author = "Sparano, {Joseph A.} and Abdissa Negassa and Erick Lansigan and Robin Locke and {De Silva}, {Chamath R.} and Wiernik, {Peter H.}",
year = "2005",
month = "9",
doi = "10.1385/MO:22:3:257",
language = "English (US)",
volume = "22",
pages = "257--267",
journal = "Medical Oncology and Tumor Pharmacotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "3",

}

TY - JOUR

T1 - Phase I trial of infusional cyclophosphamide, doxorubicin, and etoposide plus Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in non-Hodgkin's lymphoma

AU - Sparano, Joseph A.

AU - Negassa, Abdissa

AU - Lansigan, Erick

AU - Locke, Robin

AU - De Silva, Chamath R.

AU - Wiernik, Peter H.

PY - 2005/9

Y1 - 2005/9

N2 - Purpose: To determine the recommended phase II dose (RPTD) of a 96-h continuous intravenous infusion (CIVI) of cyclophosphamide (200, 300, or 400 mg/m2/d) and etoposide (60 or 90 mg/m2/d) when used in conjunction with doxorubicin (12.5 mg/m2/d) (CDE) given every 28 d plus granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with poor prognosis non-Hodgkin's lymphoma (Group A), and the same regimen given every 21 d (Group B). Methods: In Group A, infusional CDE was repeated every 28 d, GM-CSF (250 μg/m2) was given subcutaneously from d 6 until neutrophil recovery, with dose escalation in cohorts of three to six evaluable patients. The RPTD of cyclophosphamide and etoposide established in Group A was then used with CDE given every 3 wk (Group B) with GM-CSF given on d 6-20, and dose escalation was attempted again. Results: In Group A, the RPTD of cyclophosphamide and etoposide were 300 mg/m2/d and 90 mg/m 2/d, respectively; prolonged neutropenia was the dose-limiting toxicity. In Group B, use of GM-CSF on d 6-20 did not facilitate dose escalation above the RPTD established in Group A. Complete response occurred in 13/26 patients (50%) with no prior chemotherapy, and in 4/16 patients (25%) who had relapsed after prior chemotherapy. Conclusions: Because of the increase in dose and dose-density afforded by the administration of GM-CSF, the relative dose intensity was increased by twofold for cyclophosphamide (400 vs 200 mg/m 2/wk) and etoposide (120 vs 60 mg/m2/wk), and by 1.3-fold for doxorubicin (16.7 vs 12.5 mg/m2/wk).

AB - Purpose: To determine the recommended phase II dose (RPTD) of a 96-h continuous intravenous infusion (CIVI) of cyclophosphamide (200, 300, or 400 mg/m2/d) and etoposide (60 or 90 mg/m2/d) when used in conjunction with doxorubicin (12.5 mg/m2/d) (CDE) given every 28 d plus granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with poor prognosis non-Hodgkin's lymphoma (Group A), and the same regimen given every 21 d (Group B). Methods: In Group A, infusional CDE was repeated every 28 d, GM-CSF (250 μg/m2) was given subcutaneously from d 6 until neutrophil recovery, with dose escalation in cohorts of three to six evaluable patients. The RPTD of cyclophosphamide and etoposide established in Group A was then used with CDE given every 3 wk (Group B) with GM-CSF given on d 6-20, and dose escalation was attempted again. Results: In Group A, the RPTD of cyclophosphamide and etoposide were 300 mg/m2/d and 90 mg/m 2/d, respectively; prolonged neutropenia was the dose-limiting toxicity. In Group B, use of GM-CSF on d 6-20 did not facilitate dose escalation above the RPTD established in Group A. Complete response occurred in 13/26 patients (50%) with no prior chemotherapy, and in 4/16 patients (25%) who had relapsed after prior chemotherapy. Conclusions: Because of the increase in dose and dose-density afforded by the administration of GM-CSF, the relative dose intensity was increased by twofold for cyclophosphamide (400 vs 200 mg/m 2/wk) and etoposide (120 vs 60 mg/m2/wk), and by 1.3-fold for doxorubicin (16.7 vs 12.5 mg/m2/wk).

KW - Granulocyte-macrophage colony stimulating factor

KW - Non-Hodgkin's lymphoma

UR - http://www.scopus.com/inward/record.url?scp=23844516404&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23844516404&partnerID=8YFLogxK

U2 - 10.1385/MO:22:3:257

DO - 10.1385/MO:22:3:257

M3 - Article

C2 - 16110137

AN - SCOPUS:23844516404

VL - 22

SP - 257

EP - 267

JO - Medical Oncology and Tumor Pharmacotherapy

JF - Medical Oncology and Tumor Pharmacotherapy

SN - 0340-7004

IS - 3

ER -