Immune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes.
Besides cytotoxicity, taxanes induce other biological effects, especially in the immune system. Taxanes have demonstrated immunostimulatory effects against neoplasms, supporting the idea that these agents suppress cancer through several mechanisms and not solely through inhibiting cell division. The purpose of the present study was to evaluate the effect of taxanes (paclitaxel and docetaxel) and investigate their ability in alterating important immunological parameters in breast cancer patients. Thirty women with advanced breast cancer undergoing chemotherapy were randomly assigned into two groups treated with either single agent Paclitaxel or Docetaxel. Sera from patients before the first and after the last treatment cycle and from normal donors were assayed by ELISA for IL-2, IL-1beta, IFN-gamma, GM-CSF, IL-6, TNF-alpha, and PGE2 levels. In these same blood samples, NK and LAK cell activity was tested in the total PBMC population against NK-sensitive K562 tumour targets, respectively, and autologous mixed lymphocyte reaction was tested by (3)H-thymidine proliferation assays. All patients in both groups responded to therapy. Significant differences were observed in the following immune parameters between the control group of healthy blood donors and the pretreatment values of both taxane groups; IL-2, GM-CSF, IFN-gamma levels and NK and LAK cell cytotoxicity were depressed, whereas TNF-alpha and IL-6 levels were raised in breast cancer patients before treatment compared to controls. There were no significant differences between the two treatment groups regarding any of the parameters studied. Both drugs led to increases in MLR values, NK and LAK cell cytotoxicity, and IL-6, GM-CSF, IFN-gamma levels, and decreases for IL-1, TNF, and PGE2 levels. The percentage of these differences was greater for docetaxel in comparison to paclitaxel (P<0.0001). More specifically, docetaxel demonstrated a more pronounced effect on enhancing MLR, NK, LAK activity and IFN-gamma, IL-2, IL-6, and GM-CSF levels, as well as caused more potent reduction in IL-1 and TNF-alpha levels when compared to paclitaxel. The present study indicates that patients responded to treatment of advanced breast cancer with single-agent paclitaxel or docetaxel leads to an increase in serum IFN-gamma, IL-2, IL-6, GM-CSF cytokine levels and enhancement of PBMC NK and LAK cell activity, while they both lead to a decrease of acute phase serum cytokine levels of IL-1 and TNF-alpha. Moreover, the effects of docetaxel are in all the above parameters more pronounced than those of paclitaxel.
Tsavaris
N
N
Department of Pathophysiology-Oncology Unit, Laikon General Hospital, Athens University School of Medicine, 11527 Athens, Greece. tsavari1@otenet.gr
Kosmas
C
C
Vadiaka
M
M
Kanelopoulos
P
P
Boulamatsis
D
D
D000328:Adult; D000917:Antibody Formation / Q000187:drug effects; D000972:Antineoplastic Agents, Phytogenic / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D016207:Cytokines / Q000032:analysis* / Q000276:immunology; D000077143:Docetaxel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006133:Growth Substances / Q000032:analysis*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology*; D008875:Middle Aged; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D043823:Taxoids
D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D006133:Growth Substances; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel