Phase I trial of granulocyte macrophage-colony stimulating factor and interleukin-4 as a combined immunotherapy for patients with cancer
| Autor: | Frances Rosen, Nancy Moldawer, Robert A. Figlin, Barbara J. Gitlitz, Sylvia M. Kiertscher, Michael D. Roth |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Male Cancer Research Maximum Tolerated Dose Microgram medicine.medical_treatment Immunology Population Pharmacology Risk Assessment Drug Administration Schedule Cohort Studies Neoplasms medicine Immunology and Allergy Humans education Interleukin 4 Aged Neoplasm Staging education.field_of_study Dose-Response Relationship Drug business.industry Interleukin Granulocyte-Macrophage Colony-Stimulating Factor Immunotherapy Middle Aged Prognosis Combined Modality Therapy Survival Analysis Granulocyte macrophage colony-stimulating factor Cytokine Treatment Outcome Female Interleukin-4 business Ex vivo medicine.drug |
| Zdroj: | Journal of immunotherapy (Hagerstown, Md. : 1997). 26(2) |
| ISSN: | 1524-9557 |
| Popis: | Antigen-presenting cells (APC), such as dendritic cells (DC), are the key component of many cancer immunotherapy strategies. However, DCs comprise a rare population of clinically obtainable cells and are compromised in function in cancer-bearing hosts. Clinical trials therefore rely upon DC generated ex vivo. The authors hypothesized that systemic administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin (IL)-4 might lead to the differentiation of DC from their precursors and enhance their number and function in vivo, as it does in vitro. Subjects with advanced malignancies were treated in this phase I, multiple cohort, dose-escalation trial combining GM-CSF (2.5 microgram/kg/d) plus IL-4 (0-6.0 microgram/kg/d). A cycle consisted of 14 days of cytokine therapy and 14 days of observation (cohorts A-D), or alternating 7-day treatment and observation periods (cohort E). Subjects were followed clinically to determine a maximally tolerated dose (MTD), and complimentary in vitro studies were performed to determine a biologically active dose (BAD). Twenty-one subjects received treatment on this outpatient-based protocol. Treatment was well tolerated and generally characterized by Grade 1 and 2 cytokine related toxicities. The MTD was determined to be GM-CSF 2.5 microgram/kg/d plus IL-4 6.0 microgram/kg/d (cohort E). Treatment in cohort D (GM-CSF 2.5 microgram/kg/d plus IL-4 4.0 microgram/kg/d) was well tolerated and resulted in a BAD. Systemic GM-CSF plus IL-4 provides a mechanism for increasing the number and function of APC in cancer patients. Future clinical applications of this strategy are numerous and include the potential as a strong vaccine adjuvant. |
| Databáze: | OpenAIRE |
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