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Preservation of immune effector cell function following administration of a dose-intense 5-fluorouracil-chemotherapy regimen.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 1993; Vol. 36 (3), pp. 185-90. - Publication Year :
- 1993
-
Abstract
- In a phase II clinical trial of 5-fluorouracil (5FU) plus N-(phosphonacetyl)-L-aspartate (PALA) therapy administration, a number of slowly developing clinical responses were observed. Because of this, a variety of immune parameters were sequentially studied in 21 patients on this trial. Of the 21 patients studied, 20 provided sufficient samples to compare baseline with subsequent values, 10 of the 20 patients responded to treatment. Responders and non-responders did not differ in any studied parameter at baseline. After 2 months of therapy, non-specific monocyte cytotoxicity (NSMC), antibody-dependent monocyte cytotoxicity (ADMC) and natural killer (NK) activity were higher in the entire study population, but these increases were not statistically significant. When responders and non-responders were evaluated separately, it was apparent that the trend was due solely to the changes observed in the responding patient population. When mean lysis values for each patient group were determined for each studied time point, it was possible to generate a mean area under the cytotoxicity/time curve (AUC) for each studied parameter. NSMC and ADMC did not differ in responders and non-responders. However, NK activity was significantly greater by mean AUC analysis (P = 0.006) in the responding group; NK activity was maintained in the responders, but decreased in non-responders. When lymphocyte and monocyte expression of the surface markers beta 2-microglobulin, HLA-DR, CD56, HNK-1, CD16 and interleukin-2 receptor were evaluated, there were no differences among responders and non-responders at baseline by mean AUC analysis or when comparing baseline with non-baseline values. It is concluded that although baseline immunological characteristics do not identify patients who are likely to respond to weekly 5FU and PALA, treatment is not associated with deleterious effects on the immune effector function parameters evaluated in this study, there being no effects on expression of a variety of associated cell-surface molecules.
- Subjects :
- Adenocarcinoma blood
Adenocarcinoma drug therapy
Antibody-Dependent Cell Cytotoxicity drug effects
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Aspartic Acid analogs & derivatives
Aspartic Acid pharmacology
Colorectal Neoplasms blood
Colorectal Neoplasms drug therapy
Dose-Response Relationship, Drug
Fluorouracil administration & dosage
Humans
Immunity, Cellular drug effects
Immunity, Cellular immunology
Interleukin-2 pharmacology
Killer Cells, Natural drug effects
Killer Cells, Natural immunology
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear immunology
Lymphocytes drug effects
Lymphocytes immunology
Monocytes drug effects
Monocytes immunology
Phenotype
Phosphonoacetic Acid analogs & derivatives
Phosphonoacetic Acid pharmacology
Adenocarcinoma immunology
Colorectal Neoplasms immunology
Fluorouracil pharmacology
Immunosuppressive Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0340-7004
- Volume :
- 36
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 8439979
- Full Text :
- https://doi.org/10.1007/BF01741090