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 journalArticlepeer-review

39 Scopus citations


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
Issue number2
StatePublished - 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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