Phase I/II study of sequential chemoimmunotherapy (SCIT) for metastatic melanoma: outpatient treatment with dacarbazine, granulocyte-macrophage colony-stimulating factor, low-dose interleukin-2, and interferon-alpha

2002 ◽  
Vol 51 (11) ◽  
pp. 630-636 ◽  
Author(s):  
Gerard Groenewegen ◽  
Andries Bloem ◽  
Gijsbert C. de Gast
Keyword(s):  
Phase I ◽  
Metastatic Melanoma ◽  
Interferon Alpha ◽  
Outpatient Treatment ◽  
Low Dose ◽  
Interleukin 2 ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Low-Dose Outpatient Chemobiotherapy With Temozolomide, Granulocyte-Macrophage Colony Stimulating Factor, Interferon-α2b, and Recombinant Interleukin-2 for the Treatment of Metastatic Melanoma

2005 ◽  
Vol 23 (35) ◽  
pp. 8992-9000 ◽  
Author(s):  
Robert W. Weber ◽  
Steven O'Day ◽  
Madalene Rose ◽  
Regina Deck ◽  
Patricia Ames ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Low Dose ◽  
Single Agent ◽  
Interleukin 2 ◽  
High Dose ◽  
Colony Stimulating Factor ◽  
Recombinant Interleukin 2 ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Purpose The objective of this study was to further investigate the efficacy and safety of low-dose outpatient chemobiotherapy in patients with unresectable metastatic melanoma. Patients and Methods Thirty-one patients with histologically confirmed unresectable measurable metastatic melanoma were enrolled onto an open-label, multicenter phase II study. The treatment regimen consisted of oral temozolomide followed by subcutaneous biotherapy with granulocyte macrophage colony-stimulating factor, interferon-alfa, and recombinant interleukin-2 (rIL-2). Results Twenty-eight patients (90%) had M1c disease, and 58% had three or more sites of metastasis. Four patients (13%), all with M1c disease, had a complete response, and four patients had a partial response. The median progression-free survival was 4.9 months and the median overall survival was 13.1 months. Two patients (6%) developed CNS metastasis as the first site of disease progression, and 7 (23%) of 30 experienced CNS progression after receiving chemobiotherapy. A total of 112 cycles of therapy were administered. Toxicity occurred in 78% of the cycles and was grade 1 or 2 in the majority of cases and easily managed. Grade 4 toxicity occurred in 3% of the cycles. Conclusion This low-dose chemobiotherapy combination produces clinical responses in patients with metastatic melanoma, even in those with M1c disease, is well tolerated, and allows home dosing. It offers a reasonable alternative to high-dose regimens, such as high-dose biochemotherapy or rIL-2 requiring prolonged periods of hospitalization, or single agent outpatient regimens, such as dacarbazine, which is usually not effective in patients with M1c disease. Furthermore, it may protect against the development of brain metastases.

PImmunotherapy of renal cell carcinoma with granulocyte macrophage colony stimulating factor and very low dose interleukin-2

2005 ◽  
Author(s):  
Pierpaolo Correale ◽  
Stefania Marsili ◽  
Marianna Sabatino ◽  
Francesco Montagnani ◽  
Giorgio Giorgi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Low Dose ◽  
Interleukin 2 ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals 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

2010 ◽  
Vol 28 (7) ◽  
pp. 1196-1202 ◽  
Author(s):  
Krishna S. Gunturu ◽  
Kenneth R. Meehan ◽  
Todd A. Mackenzie ◽  
Todd S. Crocenzi ◽  
David McDermott ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Interleukin 2 ◽  
High Dose ◽  
Memory Cells ◽  
Colony Stimulating Factor ◽  
Regulatory Cells ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Purpose 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. Patients and Methods 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/m2, 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 μg/m2/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). Results 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 regulatory cells (CD4+ T regulatory cells; CD8+ T suppressor cells) and of T memory cells (CD8+ T central memory cells; T effector memory RA+ cells). Expansion of circulating melanoma-specific CD8+ cells was observed in one of four HLA-A2-positive patients. Conclusion Chemotherapy-induced lymphodepletion modulates the homeostatic repopulation of the lymphocyte compartment and influences recovering lymphocyte subpopulations. Clinical activity seems similar to standard high-dose aldesleukin alone.

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