Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer

Jeffrey Crawford, Howard Ozer, Ronald Stoller, David Johnson, Gary Lyman, Imad Tabbara, Mark Kris, John Grous, Vincent Picozzi, Gregory Rausch, Roy Smith, William Gradishar, Anne Yahanda, Martha Vincent, Morgan Stewart, John Glaspy

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Abstract

Background. Neutropenia and infection are major dose-limiting side effects of chemotherapy. Previous studies have suggested that recombinant methionyl granulocyte colony-stimulating factor (G-CSF) can reduce chemotherapy-related neutropenia in patients with cancer. We conducted a randomized clinical trial to test this hypothesis and the clinical implications. Methods. Patients with small-cell lung cancer were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of recombinant methionyl G-CSF to study the incidence of infection as manifested by fever with neutropenia (absolute neutrophil count, < 1.0×109 per liter, with a temperature ≥38.2°C) resulting from up to six cycles of chemotherapy with cyclophosphamide, doxorubicin, and etoposide. The patients were randomly assigned to receive either placebo or G-CSF, with treatment beginning on day 4 and continuing through day 17 of a 21-day cycle. Results. The safety of the study treatment could be evaluated in 207 of the 211 patients assigned to either drug, and its efficacy in 199. At least one episode of fever with neutropenia occurred in 77 percent of the placebo group, as compared with 40 percent of the G-CSF group (P<0.001). Over all cycles of chemotherapy, the median duration of grade IV neutropenia (absolute neutrophil count, <0.5×109 per liter) was six days with placebo as compared with one day with G-CSF. During cycles of blinded treatment, the number of days of treatment with intravenous antibiotics, the number of days of hospitalization, and the incidence of confirmed infections were reduced by approximately 50 percent when G-CSF was given, as compared with placebo. Mild-to-moderate medullary bone pain occurred in 20 percent of the patients receiving G-CSF. Conclusions. The use of G-CSF as an adjunct to chemotherapy in patients with small-cell cancer of the lung was well tolerated and led to reductions in the incidence of fever with neutropenia and culture-confirmed infections; in the incidence, duration, and severity of grade IV neutropenia; and in the total number of days of treatment with intravenous antibiotics and days of hospitalization.

Original languageEnglish (US)
Pages (from-to)164-170
Number of pages7
JournalNew England Journal of Medicine
Volume325
Issue number3
StatePublished - Jul 18 1991

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Small Cell Lung Carcinoma
Granulocyte Colony-Stimulating Factor
Neutropenia
Fever
Drug Therapy
Placebos
Infection
Incidence
Hospitalization
Neutrophils
Anti-Bacterial Agents
Therapeutics
Etoposide
Doxorubicin
Cyclophosphamide
Cohort Studies
Randomized Controlled Trials
Safety
Bone and Bones
Pain

ASJC Scopus subject areas

  • Medicine(all)

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Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. / Crawford, Jeffrey; Ozer, Howard; Stoller, Ronald; Johnson, David; Lyman, Gary; Tabbara, Imad; Kris, Mark; Grous, John; Picozzi, Vincent; Rausch, Gregory; Smith, Roy; Gradishar, William; Yahanda, Anne; Vincent, Martha; Stewart, Morgan; Glaspy, John.

In: New England Journal of Medicine, Vol. 325, No. 3, 18.07.1991, p. 164-170.

Research output: Contribution to journalArticle

Crawford, J, Ozer, H, Stoller, R, Johnson, D, Lyman, G, Tabbara, I, Kris, M, Grous, J, Picozzi, V, Rausch, G, Smith, R, Gradishar, W, Yahanda, A, Vincent, M, Stewart, M & Glaspy, J 1991, 'Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer', New England Journal of Medicine, vol. 325, no. 3, pp. 164-170.
Crawford, Jeffrey ; Ozer, Howard ; Stoller, Ronald ; Johnson, David ; Lyman, Gary ; Tabbara, Imad ; Kris, Mark ; Grous, John ; Picozzi, Vincent ; Rausch, Gregory ; Smith, Roy ; Gradishar, William ; Yahanda, Anne ; Vincent, Martha ; Stewart, Morgan ; Glaspy, John. / Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. In: New England Journal of Medicine. 1991 ; Vol. 325, No. 3. pp. 164-170.
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abstract = "Background. Neutropenia and infection are major dose-limiting side effects of chemotherapy. Previous studies have suggested that recombinant methionyl granulocyte colony-stimulating factor (G-CSF) can reduce chemotherapy-related neutropenia in patients with cancer. We conducted a randomized clinical trial to test this hypothesis and the clinical implications. Methods. Patients with small-cell lung cancer were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of recombinant methionyl G-CSF to study the incidence of infection as manifested by fever with neutropenia (absolute neutrophil count, < 1.0×109 per liter, with a temperature ≥38.2°C) resulting from up to six cycles of chemotherapy with cyclophosphamide, doxorubicin, and etoposide. The patients were randomly assigned to receive either placebo or G-CSF, with treatment beginning on day 4 and continuing through day 17 of a 21-day cycle. Results. The safety of the study treatment could be evaluated in 207 of the 211 patients assigned to either drug, and its efficacy in 199. At least one episode of fever with neutropenia occurred in 77 percent of the placebo group, as compared with 40 percent of the G-CSF group (P<0.001). Over all cycles of chemotherapy, the median duration of grade IV neutropenia (absolute neutrophil count, <0.5×109 per liter) was six days with placebo as compared with one day with G-CSF. During cycles of blinded treatment, the number of days of treatment with intravenous antibiotics, the number of days of hospitalization, and the incidence of confirmed infections were reduced by approximately 50 percent when G-CSF was given, as compared with placebo. Mild-to-moderate medullary bone pain occurred in 20 percent of the patients receiving G-CSF. Conclusions. The use of G-CSF as an adjunct to chemotherapy in patients with small-cell cancer of the lung was well tolerated and led to reductions in the incidence of fever with neutropenia and culture-confirmed infections; in the incidence, duration, and severity of grade IV neutropenia; and in the total number of days of treatment with intravenous antibiotics and days of hospitalization.",
author = "Jeffrey Crawford and Howard Ozer and Ronald Stoller and David Johnson and Gary Lyman and Imad Tabbara and Mark Kris and John Grous and Vincent Picozzi and Gregory Rausch and Roy Smith and William Gradishar and Anne Yahanda and Martha Vincent and Morgan Stewart and John Glaspy",
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T1 - Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer

AU - Crawford, Jeffrey

AU - Ozer, Howard

AU - Stoller, Ronald

AU - Johnson, David

AU - Lyman, Gary

AU - Tabbara, Imad

AU - Kris, Mark

AU - Grous, John

AU - Picozzi, Vincent

AU - Rausch, Gregory

AU - Smith, Roy

AU - Gradishar, William

AU - Yahanda, Anne

AU - Vincent, Martha

AU - Stewart, Morgan

AU - Glaspy, John

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N2 - Background. Neutropenia and infection are major dose-limiting side effects of chemotherapy. Previous studies have suggested that recombinant methionyl granulocyte colony-stimulating factor (G-CSF) can reduce chemotherapy-related neutropenia in patients with cancer. We conducted a randomized clinical trial to test this hypothesis and the clinical implications. Methods. Patients with small-cell lung cancer were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of recombinant methionyl G-CSF to study the incidence of infection as manifested by fever with neutropenia (absolute neutrophil count, < 1.0×109 per liter, with a temperature ≥38.2°C) resulting from up to six cycles of chemotherapy with cyclophosphamide, doxorubicin, and etoposide. The patients were randomly assigned to receive either placebo or G-CSF, with treatment beginning on day 4 and continuing through day 17 of a 21-day cycle. Results. The safety of the study treatment could be evaluated in 207 of the 211 patients assigned to either drug, and its efficacy in 199. At least one episode of fever with neutropenia occurred in 77 percent of the placebo group, as compared with 40 percent of the G-CSF group (P<0.001). Over all cycles of chemotherapy, the median duration of grade IV neutropenia (absolute neutrophil count, <0.5×109 per liter) was six days with placebo as compared with one day with G-CSF. During cycles of blinded treatment, the number of days of treatment with intravenous antibiotics, the number of days of hospitalization, and the incidence of confirmed infections were reduced by approximately 50 percent when G-CSF was given, as compared with placebo. Mild-to-moderate medullary bone pain occurred in 20 percent of the patients receiving G-CSF. Conclusions. The use of G-CSF as an adjunct to chemotherapy in patients with small-cell cancer of the lung was well tolerated and led to reductions in the incidence of fever with neutropenia and culture-confirmed infections; in the incidence, duration, and severity of grade IV neutropenia; and in the total number of days of treatment with intravenous antibiotics and days of hospitalization.

AB - Background. Neutropenia and infection are major dose-limiting side effects of chemotherapy. Previous studies have suggested that recombinant methionyl granulocyte colony-stimulating factor (G-CSF) can reduce chemotherapy-related neutropenia in patients with cancer. We conducted a randomized clinical trial to test this hypothesis and the clinical implications. Methods. Patients with small-cell lung cancer were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of recombinant methionyl G-CSF to study the incidence of infection as manifested by fever with neutropenia (absolute neutrophil count, < 1.0×109 per liter, with a temperature ≥38.2°C) resulting from up to six cycles of chemotherapy with cyclophosphamide, doxorubicin, and etoposide. The patients were randomly assigned to receive either placebo or G-CSF, with treatment beginning on day 4 and continuing through day 17 of a 21-day cycle. Results. The safety of the study treatment could be evaluated in 207 of the 211 patients assigned to either drug, and its efficacy in 199. At least one episode of fever with neutropenia occurred in 77 percent of the placebo group, as compared with 40 percent of the G-CSF group (P<0.001). Over all cycles of chemotherapy, the median duration of grade IV neutropenia (absolute neutrophil count, <0.5×109 per liter) was six days with placebo as compared with one day with G-CSF. During cycles of blinded treatment, the number of days of treatment with intravenous antibiotics, the number of days of hospitalization, and the incidence of confirmed infections were reduced by approximately 50 percent when G-CSF was given, as compared with placebo. Mild-to-moderate medullary bone pain occurred in 20 percent of the patients receiving G-CSF. Conclusions. The use of G-CSF as an adjunct to chemotherapy in patients with small-cell cancer of the lung was well tolerated and led to reductions in the incidence of fever with neutropenia and culture-confirmed infections; in the incidence, duration, and severity of grade IV neutropenia; and in the total number of days of treatment with intravenous antibiotics and days of hospitalization.

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