Cytokine working group study of lymphodepleting chemotherapy, interleukin-2, and granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma: clinical outcomes and peripheral-blood cell recovery.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Krishna S GunturuMarc S Ernstoff

Abstract

Recovery of lymphocyte populations after lymphocyte depletion is implicated in therapeutic immune pathways in animal models and in patients with cancer. We sought to evaluate the effects of chemotherapy-induced lymphodepletion followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) and high-dose interleukin-2 (IL-2) therapy on clinical response and the recovery of lymphocyte subcompartments in patients with metastatic melanoma. This was a two-stage phase II trial design. Patients with measurable metastatic melanoma were treated with intravenous cyclophosphamide (60 mg/kg, days 1 and 2) and fludarabine (25 mg/m(2), day 3 through 7) followed by two 5-day courses of intravenous high-dose bolus IL-2 (600,000 U/kg; days 8 through 12 and 21 through 25). GM-CSF (250 microg/m(2)/d beginning day 8) was given until granulocyte recovery. Lymphocyte recovery profiles were determined by flow cytometric phenotyping at regular intervals, and clinical outcome was assessed by Response Evaluation Criteria in Solid Tumors (RECIST). The trial was stopped at the end of stage 1 with four of 18 objective responses noted. Twelve patients had detailed lymphocyte subcompartments evaluated. After lymphodepletion, we observed an induction of...Continue Reading

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Citations

Mar 2, 2011·Cancer Biotherapy & Radiopharmaceuticals·Robert O Dillman
May 11, 2011·Immunotherapy·Courtney Nicholas, Gregory B Lesinski
Mar 7, 2014·Current Treatment Options in Oncology·Ahmed I Megahed, Henry B Koon
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Mar 11, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Harry DolstraNicolaas M Schaap

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