title: Preservation of immune effector cell function following administration of a dose-intense 5-fluorouracil-chemotherapy regimen.
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.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: L M
authors.initials: LM
authors.lastname: Weiner
authors.forename: G R
authors.initials: GR
authors.lastname: Hudes
authors.forename: J
authors.initials: J
authors.lastname: Kitson
authors.forename: J
authors.initials: J
authors.lastname: Walczak
authors.forename: P
authors.initials: P
authors.lastname: Watts
authors.forename: S
authors.initials: S
authors.lastname: Litwin
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Dwyer
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010641:Phenotype; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D007376:Interleukin-2; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D005472:Fluorouracil