Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells

A novel and effective method for delivering multiple courses of dose-intensive therapy

Thomas C. Shea, James R. Mason, Anna Maria Storniolo, Barbara Newton, Margaret Breslin, Michael Mullen, David M. Ward, Langdon Miller, Michelle Christian, Raymond Taetle

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Purpose: The trial was undertaken to study the effect of administering granulocyte-macrophage colony-stimulating factor (GM-CSF) with and without peripheral-blood progenitor cells (PBPC) on the hematologic and nonhematologic toxicity observed with multiple cycles of high-dose carboplatin chemotherapy. Patients and Methods: Eighteen patients with a variety of solid tumors received a total of 40 cycles of carboplatin, 1,200 mg/m2 per cycle, administered by continuous infusion over 96 hours. All 40 courses were administered with a daily 4-hour intravenous (IV) infusion of either 5 or 10 μg/kg/d of recombinant human Escherichia coli-derived GM-CSF. The first 20 courses were administered without PBPC support (treatment A). Because of severe neutropenia and thrombocytopenia, the next 20 courses of therapy were administered with GM-CSF, PBPC, and oral antibiotic prophylaxis (treatment B). Results: The addition of PBPC support led to a significant reduction in the duration of neutropenia (10.5 v 7.5 days; P = .027) and thrombocytopenia (12.4 v 5.2 days; P = .001), number of RBC transfusions (six v three; P = .01) and platelet transfusions (10.3 v 3.7; P = .013), number of hospital days (12.6 v 2.9; P = .01), and days of IV antibiotics (11.8 v 2.4; P = .007) per cycle. Significant increases in the weekly dose intensity (206 v 285 mg/m2/ wk; P = .014) and total dose (2,287 v 3,600 mg/m2; P = .018) of carboplatin delivered were also observed with treatment B. The overall response rate in this study was 70%, with 11 of 16 assessable patients achieving either a complete (three patients) or partial (eight patients) remission. Conclusion: This combination of GM-CSF and PBPC infusion represents an effective method for delivering multiple cycles of high-dose carboplatin chemotherapy and may serve as a model for the administration of high-dose chemotherapy in future trials.

Original languageEnglish (US)
Pages (from-to)464-473
Number of pages10
JournalJournal of Clinical Oncology
Volume10
Issue number3
StatePublished - 1992
Externally publishedYes

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Carboplatin
Granulocyte-Macrophage Colony-Stimulating Factor
Blood Cells
Stem Cells
Neutropenia
Drug Therapy
Thrombocytopenia
Therapeutics
Platelet Transfusion
Antibiotic Prophylaxis
Intravenous Infusions
Escherichia coli
Anti-Bacterial Agents
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells : A novel and effective method for delivering multiple courses of dose-intensive therapy. / Shea, Thomas C.; Mason, James R.; Storniolo, Anna Maria; Newton, Barbara; Breslin, Margaret; Mullen, Michael; Ward, David M.; Miller, Langdon; Christian, Michelle; Taetle, Raymond.

In: Journal of Clinical Oncology, Vol. 10, No. 3, 1992, p. 464-473.

Research output: Contribution to journalArticle

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title = "Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells: A novel and effective method for delivering multiple courses of dose-intensive therapy",
abstract = "Purpose: The trial was undertaken to study the effect of administering granulocyte-macrophage colony-stimulating factor (GM-CSF) with and without peripheral-blood progenitor cells (PBPC) on the hematologic and nonhematologic toxicity observed with multiple cycles of high-dose carboplatin chemotherapy. Patients and Methods: Eighteen patients with a variety of solid tumors received a total of 40 cycles of carboplatin, 1,200 mg/m2 per cycle, administered by continuous infusion over 96 hours. All 40 courses were administered with a daily 4-hour intravenous (IV) infusion of either 5 or 10 μg/kg/d of recombinant human Escherichia coli-derived GM-CSF. The first 20 courses were administered without PBPC support (treatment A). Because of severe neutropenia and thrombocytopenia, the next 20 courses of therapy were administered with GM-CSF, PBPC, and oral antibiotic prophylaxis (treatment B). Results: The addition of PBPC support led to a significant reduction in the duration of neutropenia (10.5 v 7.5 days; P = .027) and thrombocytopenia (12.4 v 5.2 days; P = .001), number of RBC transfusions (six v three; P = .01) and platelet transfusions (10.3 v 3.7; P = .013), number of hospital days (12.6 v 2.9; P = .01), and days of IV antibiotics (11.8 v 2.4; P = .007) per cycle. Significant increases in the weekly dose intensity (206 v 285 mg/m2/ wk; P = .014) and total dose (2,287 v 3,600 mg/m2; P = .018) of carboplatin delivered were also observed with treatment B. The overall response rate in this study was 70{\%}, with 11 of 16 assessable patients achieving either a complete (three patients) or partial (eight patients) remission. Conclusion: This combination of GM-CSF and PBPC infusion represents an effective method for delivering multiple cycles of high-dose carboplatin chemotherapy and may serve as a model for the administration of high-dose chemotherapy in future trials.",
author = "Shea, {Thomas C.} and Mason, {James R.} and Storniolo, {Anna Maria} and Barbara Newton and Margaret Breslin and Michael Mullen and Ward, {David M.} and Langdon Miller and Michelle Christian and Raymond Taetle",
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T1 - Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells

T2 - A novel and effective method for delivering multiple courses of dose-intensive therapy

AU - Shea, Thomas C.

AU - Mason, James R.

AU - Storniolo, Anna Maria

AU - Newton, Barbara

AU - Breslin, Margaret

AU - Mullen, Michael

AU - Ward, David M.

AU - Miller, Langdon

AU - Christian, Michelle

AU - Taetle, Raymond

PY - 1992

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N2 - Purpose: The trial was undertaken to study the effect of administering granulocyte-macrophage colony-stimulating factor (GM-CSF) with and without peripheral-blood progenitor cells (PBPC) on the hematologic and nonhematologic toxicity observed with multiple cycles of high-dose carboplatin chemotherapy. Patients and Methods: Eighteen patients with a variety of solid tumors received a total of 40 cycles of carboplatin, 1,200 mg/m2 per cycle, administered by continuous infusion over 96 hours. All 40 courses were administered with a daily 4-hour intravenous (IV) infusion of either 5 or 10 μg/kg/d of recombinant human Escherichia coli-derived GM-CSF. The first 20 courses were administered without PBPC support (treatment A). Because of severe neutropenia and thrombocytopenia, the next 20 courses of therapy were administered with GM-CSF, PBPC, and oral antibiotic prophylaxis (treatment B). Results: The addition of PBPC support led to a significant reduction in the duration of neutropenia (10.5 v 7.5 days; P = .027) and thrombocytopenia (12.4 v 5.2 days; P = .001), number of RBC transfusions (six v three; P = .01) and platelet transfusions (10.3 v 3.7; P = .013), number of hospital days (12.6 v 2.9; P = .01), and days of IV antibiotics (11.8 v 2.4; P = .007) per cycle. Significant increases in the weekly dose intensity (206 v 285 mg/m2/ wk; P = .014) and total dose (2,287 v 3,600 mg/m2; P = .018) of carboplatin delivered were also observed with treatment B. The overall response rate in this study was 70%, with 11 of 16 assessable patients achieving either a complete (three patients) or partial (eight patients) remission. Conclusion: This combination of GM-CSF and PBPC infusion represents an effective method for delivering multiple cycles of high-dose carboplatin chemotherapy and may serve as a model for the administration of high-dose chemotherapy in future trials.

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