Clinical and immimological effects of granulocyte-macrophage colony-stimulating factor coadministered with interleukin 2: A phase IB study

Joan H. Schiller, Jacquelyn A. Hank, Masoud Khorsand, Barry Storer, Agnes Borchert, Karen Huseby-Moore, Dan Burns, Osvaldo Wesly, Mark R. Albertini, George Wilding, Paul M. Sondel

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Interleukin 2 (IL-2) and granulocytes-macrophage colony-stimulating factor (GM-CSF) are activators of the lymphocyte and granulocyte/macrophage series, respectively. We conducted a phase IB trial to identify the maximally tolerated dose and to assess immunological effects of the combination. Thirty-four patients with incurable cancers received 2.5, 5, or 10 μg/kg GM-CSF s.c. either before or concurrently with 1.5 or 3.0 million units/m2/day IL-2. The most common laboratory and clinical side effects included an elevation of the total WBC or eosinophil count due to GM-CSF, and constitutional symptoms due to IL-2. Grade 3 or 4 toxicities included hypotension, thrombocytopenia, elevations in aspartate aminotransferase or bilirubin, renal toxicity, gastrointestinal hemorrhage, arrhythmia, and constitutional symptoms. Two patients receiving 5.0 μg/kg GM-CSF plus concurrent 3.0 million units IL-2 experienced dose-limiting grade 3 or 4 neurological toxicity, which reversed almost completely. An increase in the serum-solubie IL-2 α chain receptor was observed with administration of GM-CSF, IL-2, or the combination. IL-2 therapy enhanced lymphokine-activated killer activity, antibody-dependent cellular cytotoxicity, and lymphocyte activation, with increased CD16 and CD56 expression. GM-CSF increased expression of human leukocyte antigen DR on peripheral blood monocytes and decreased surface expression of CD16 on circulating monocytes and pohmorphonuclear cells. Lymphokine-activated killer activity and CD16 expression on monocytes and lymphocytes and CD56 expression on lymphocytes were significantly lower in patients receiving GM-CSF simultaneously with IL-2 than in patients receiving the sequential treatment. Antitumor activity was observed in the lungs of four of eight renal cell carcinoma patients with pulmonary metastases treated with concurrent GM-CSF and IL-2. Although no or minimal shrinkage was observed in the patients' large primary tumors, these results warrant further study. The recommended initial Phase II dose and schedule is 1.25 μg/kg/day GM-CSF, given concurrently with 1.5 million Roche units/m2/day (4.5 × 106 international units/m2/day) IL-2, with subsequent escalation of GM-CSF to 2.5 μg/kg/ day after careful observation for toxicities.

Original languageEnglish (US)
Pages (from-to)319-330
Number of pages12
JournalClinical Cancer Research
Volume2
Issue number2
StatePublished - 1996

Fingerprint

Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-2
Monocytes
Lymphokines
Lymphocytes
Lung
Gastrointestinal Hemorrhage
Maximum Tolerated Dose
Interleukin-2 Receptors
Lymphocyte Activation
HLA Antigens
Aspartate Aminotransferases
Bilirubin
Renal Cell Carcinoma
Granulocytes
Eosinophils
Thrombocytopenia
Hypotension
Cardiac Arrhythmias
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Schiller, J. H., Hank, J. A., Khorsand, M., Storer, B., Borchert, A., Huseby-Moore, K., ... Sondel, P. M. (1996). Clinical and immimological effects of granulocyte-macrophage colony-stimulating factor coadministered with interleukin 2: A phase IB study. Clinical Cancer Research, 2(2), 319-330.

Clinical and immimological effects of granulocyte-macrophage colony-stimulating factor coadministered with interleukin 2 : A phase IB study. / Schiller, Joan H.; Hank, Jacquelyn A.; Khorsand, Masoud; Storer, Barry; Borchert, Agnes; Huseby-Moore, Karen; Burns, Dan; Wesly, Osvaldo; Albertini, Mark R.; Wilding, George; Sondel, Paul M.

In: Clinical Cancer Research, Vol. 2, No. 2, 1996, p. 319-330.

Research output: Contribution to journalArticle

Schiller, JH, Hank, JA, Khorsand, M, Storer, B, Borchert, A, Huseby-Moore, K, Burns, D, Wesly, O, Albertini, MR, Wilding, G & Sondel, PM 1996, 'Clinical and immimological effects of granulocyte-macrophage colony-stimulating factor coadministered with interleukin 2: A phase IB study', Clinical Cancer Research, vol. 2, no. 2, pp. 319-330.
Schiller, Joan H. ; Hank, Jacquelyn A. ; Khorsand, Masoud ; Storer, Barry ; Borchert, Agnes ; Huseby-Moore, Karen ; Burns, Dan ; Wesly, Osvaldo ; Albertini, Mark R. ; Wilding, George ; Sondel, Paul M. / Clinical and immimological effects of granulocyte-macrophage colony-stimulating factor coadministered with interleukin 2 : A phase IB study. In: Clinical Cancer Research. 1996 ; Vol. 2, No. 2. pp. 319-330.
@article{cb894be619e5452394b219d721925361,
title = "Clinical and immimological effects of granulocyte-macrophage colony-stimulating factor coadministered with interleukin 2: A phase IB study",
abstract = "Interleukin 2 (IL-2) and granulocytes-macrophage colony-stimulating factor (GM-CSF) are activators of the lymphocyte and granulocyte/macrophage series, respectively. We conducted a phase IB trial to identify the maximally tolerated dose and to assess immunological effects of the combination. Thirty-four patients with incurable cancers received 2.5, 5, or 10 μg/kg GM-CSF s.c. either before or concurrently with 1.5 or 3.0 million units/m2/day IL-2. The most common laboratory and clinical side effects included an elevation of the total WBC or eosinophil count due to GM-CSF, and constitutional symptoms due to IL-2. Grade 3 or 4 toxicities included hypotension, thrombocytopenia, elevations in aspartate aminotransferase or bilirubin, renal toxicity, gastrointestinal hemorrhage, arrhythmia, and constitutional symptoms. Two patients receiving 5.0 μg/kg GM-CSF plus concurrent 3.0 million units IL-2 experienced dose-limiting grade 3 or 4 neurological toxicity, which reversed almost completely. An increase in the serum-solubie IL-2 α chain receptor was observed with administration of GM-CSF, IL-2, or the combination. IL-2 therapy enhanced lymphokine-activated killer activity, antibody-dependent cellular cytotoxicity, and lymphocyte activation, with increased CD16 and CD56 expression. GM-CSF increased expression of human leukocyte antigen DR on peripheral blood monocytes and decreased surface expression of CD16 on circulating monocytes and pohmorphonuclear cells. Lymphokine-activated killer activity and CD16 expression on monocytes and lymphocytes and CD56 expression on lymphocytes were significantly lower in patients receiving GM-CSF simultaneously with IL-2 than in patients receiving the sequential treatment. Antitumor activity was observed in the lungs of four of eight renal cell carcinoma patients with pulmonary metastases treated with concurrent GM-CSF and IL-2. Although no or minimal shrinkage was observed in the patients' large primary tumors, these results warrant further study. The recommended initial Phase II dose and schedule is 1.25 μg/kg/day GM-CSF, given concurrently with 1.5 million Roche units/m2/day (4.5 × 106 international units/m2/day) IL-2, with subsequent escalation of GM-CSF to 2.5 μg/kg/ day after careful observation for toxicities.",
author = "Schiller, {Joan H.} and Hank, {Jacquelyn A.} and Masoud Khorsand and Barry Storer and Agnes Borchert and Karen Huseby-Moore and Dan Burns and Osvaldo Wesly and Albertini, {Mark R.} and George Wilding and Sondel, {Paul M.}",
year = "1996",
language = "English (US)",
volume = "2",
pages = "319--330",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "2",

}

TY - JOUR

T1 - Clinical and immimological effects of granulocyte-macrophage colony-stimulating factor coadministered with interleukin 2

T2 - A phase IB study

AU - Schiller, Joan H.

AU - Hank, Jacquelyn A.

AU - Khorsand, Masoud

AU - Storer, Barry

AU - Borchert, Agnes

AU - Huseby-Moore, Karen

AU - Burns, Dan

AU - Wesly, Osvaldo

AU - Albertini, Mark R.

AU - Wilding, George

AU - Sondel, Paul M.

PY - 1996

Y1 - 1996

N2 - Interleukin 2 (IL-2) and granulocytes-macrophage colony-stimulating factor (GM-CSF) are activators of the lymphocyte and granulocyte/macrophage series, respectively. We conducted a phase IB trial to identify the maximally tolerated dose and to assess immunological effects of the combination. Thirty-four patients with incurable cancers received 2.5, 5, or 10 μg/kg GM-CSF s.c. either before or concurrently with 1.5 or 3.0 million units/m2/day IL-2. The most common laboratory and clinical side effects included an elevation of the total WBC or eosinophil count due to GM-CSF, and constitutional symptoms due to IL-2. Grade 3 or 4 toxicities included hypotension, thrombocytopenia, elevations in aspartate aminotransferase or bilirubin, renal toxicity, gastrointestinal hemorrhage, arrhythmia, and constitutional symptoms. Two patients receiving 5.0 μg/kg GM-CSF plus concurrent 3.0 million units IL-2 experienced dose-limiting grade 3 or 4 neurological toxicity, which reversed almost completely. An increase in the serum-solubie IL-2 α chain receptor was observed with administration of GM-CSF, IL-2, or the combination. IL-2 therapy enhanced lymphokine-activated killer activity, antibody-dependent cellular cytotoxicity, and lymphocyte activation, with increased CD16 and CD56 expression. GM-CSF increased expression of human leukocyte antigen DR on peripheral blood monocytes and decreased surface expression of CD16 on circulating monocytes and pohmorphonuclear cells. Lymphokine-activated killer activity and CD16 expression on monocytes and lymphocytes and CD56 expression on lymphocytes were significantly lower in patients receiving GM-CSF simultaneously with IL-2 than in patients receiving the sequential treatment. Antitumor activity was observed in the lungs of four of eight renal cell carcinoma patients with pulmonary metastases treated with concurrent GM-CSF and IL-2. Although no or minimal shrinkage was observed in the patients' large primary tumors, these results warrant further study. The recommended initial Phase II dose and schedule is 1.25 μg/kg/day GM-CSF, given concurrently with 1.5 million Roche units/m2/day (4.5 × 106 international units/m2/day) IL-2, with subsequent escalation of GM-CSF to 2.5 μg/kg/ day after careful observation for toxicities.

AB - Interleukin 2 (IL-2) and granulocytes-macrophage colony-stimulating factor (GM-CSF) are activators of the lymphocyte and granulocyte/macrophage series, respectively. We conducted a phase IB trial to identify the maximally tolerated dose and to assess immunological effects of the combination. Thirty-four patients with incurable cancers received 2.5, 5, or 10 μg/kg GM-CSF s.c. either before or concurrently with 1.5 or 3.0 million units/m2/day IL-2. The most common laboratory and clinical side effects included an elevation of the total WBC or eosinophil count due to GM-CSF, and constitutional symptoms due to IL-2. Grade 3 or 4 toxicities included hypotension, thrombocytopenia, elevations in aspartate aminotransferase or bilirubin, renal toxicity, gastrointestinal hemorrhage, arrhythmia, and constitutional symptoms. Two patients receiving 5.0 μg/kg GM-CSF plus concurrent 3.0 million units IL-2 experienced dose-limiting grade 3 or 4 neurological toxicity, which reversed almost completely. An increase in the serum-solubie IL-2 α chain receptor was observed with administration of GM-CSF, IL-2, or the combination. IL-2 therapy enhanced lymphokine-activated killer activity, antibody-dependent cellular cytotoxicity, and lymphocyte activation, with increased CD16 and CD56 expression. GM-CSF increased expression of human leukocyte antigen DR on peripheral blood monocytes and decreased surface expression of CD16 on circulating monocytes and pohmorphonuclear cells. Lymphokine-activated killer activity and CD16 expression on monocytes and lymphocytes and CD56 expression on lymphocytes were significantly lower in patients receiving GM-CSF simultaneously with IL-2 than in patients receiving the sequential treatment. Antitumor activity was observed in the lungs of four of eight renal cell carcinoma patients with pulmonary metastases treated with concurrent GM-CSF and IL-2. Although no or minimal shrinkage was observed in the patients' large primary tumors, these results warrant further study. The recommended initial Phase II dose and schedule is 1.25 μg/kg/day GM-CSF, given concurrently with 1.5 million Roche units/m2/day (4.5 × 106 international units/m2/day) IL-2, with subsequent escalation of GM-CSF to 2.5 μg/kg/ day after careful observation for toxicities.

UR - http://www.scopus.com/inward/record.url?scp=0029916896&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029916896&partnerID=8YFLogxK

M3 - Article

C2 - 9816175

AN - SCOPUS:0029916896

VL - 2

SP - 319

EP - 330

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 2

ER -