Cisplatin-based polychemotherapy reduces the natural cytotoxicity of peripheral blood mononuclear cells in patients with advanced ovarian carcinoma and their in vitro responsiveness to interleukin-12 incubation

BACKGROUND. The aim of the current study was to evaluate the in vitro effec t of IL-12 on the natural cytotoxicity of peripheral blood mononuclear cell s (PBMCs) obtained from patients who underwent adjuvant-based cisplatin pol ychemotherapy for advanced ovarian carcinoma. The authors also investigated amifostine, a cytoprotective agent that appears to protect against chemoth erapy damage to healthy tissues, to determine its effects on natural immune function. METHODS. Twenty-one women with advanced ovarian serous cystoadenocarcinoma who underwent adjuvant cisplatin-based polychemotherapy were included in th e study, and 20 normal volunteer women matched for age served as controls. Six of the 21 women who underwent polychemotherapy received 1:3 amifostine pretreatment. Blood samples were obtained immediately before the first cycl e of cisplatin-based polychemotherapy and within 24 hours after the complet ion of polychemotherapy infusion to evaluate the natural cytotoxic activity of PBMCs against the K562 cell line and the in vitro responsiveness of cyt otoxic cells to interleukin-12 (IL-12). RESULTS. The in vivo administration of cisplatin-based polychemotherapy sig nificantly reduced the natural killer cytotoxicity of PBMCs toward undetect able levels (2.2 +/- 3.1 vs. 9.2 +/- 7.0 lytic units, respectively, after a nd before cisplatin; P < 0.01), and the in vitro exposure to IL-12 did not increase the cytolytic activity of PBMCs (1.9 +/- 2.1 lytic units). PBMCs f rom the 6 patients who received random amifostine pretreatment were shown t o have retained natural killer cytotoxicity after in vivo administration of cisplatin polychemotherapy (9.7 +/- 6.7 vs. 9.6 +/- 6.0 lyric units, respe ctively, after and before cisplatin; P = 0.9), and the incubation with IL-1 2 increased cytotoxic activity (13.4 +/- 6.9 lytic units) toward the levels observed in PBMCs of controls (14.0 +/- 4.6 lytic units). CONCLUSIONS. These data suggest that cisplatin-based polychemotherapy reduc es the natural cytotoxicity of PBMCs in patients with advanced ovarian carc inoma as well as their in vitro responsiveness to IL-12 incubation. Amifost ine demonstrated a protective effect on natural killer cell cytotoxicity an d responsiveness to IL-12 in this small cohort of patients. Cancer 1999;85: 2226-31, (C) 1999 American Cancer Society.