Assessment of Cytokine Levels in Ascitic Fluid in Patients with Ovarian Cancer Receiving Neoadjuvant Chemotherapy

For citation: Aleshikova O. I., Antonova I. B., Babaeva N. A., Gerfanova Е. V., Shendler V. O., Ashrafyan L. A. Assessment of Cytokine Levels in Ascitic Fluid in Patients with Ovarian Cancer Receiving Neoadjuvant Chemotherapy. Doctor.Ru. 2018; 2(146): 63–68.
20 February 14:44

Study Objective: To determine ascitic fluid levels of cytokines in patients with stage III–IV serous ovarian cancer (OC) before and after neoadjuvant chemotherapy (NCT) given in combination with indole-3-carbinol (I3C) and epigallocatechin gallate (EGCG).

Study Design: This was a pilot study.

Materials and Methods: Ascitic fluid was collected from 24 patients prior to specific therapy. Seven patients were unable to complete the study. The reasons were a granulosa cell tumor (GCT), secondary metastatic lesions in the ovaries, an ovarian cystadenoma, and a medical condition (hepatic cirrhosis); one patient did not receive NCT, and her samples were taken during surgery. Thus, 17 women were enrolled in the study. The average age of the patients was 59 ± 3.8.

The first step in combination treatment was a standard NCT regimen: paclitaxel 175 mg/m2 IV on day 1 and carboplatin (AUC 6) IV on day 2; the median number of courses was 4 (2–8); the courses length was 21 days. In addition to NCT all patients enrolled in the study received a drug containing I3C and EGCG, 2 capsules 3 times a day, for the entire duration of the study. In the second step of treatment, all 17 patients underwent surgery (radical hysterectomy with bilateral salpingo-oophorectomy and subtotal resection of the greater omentum).

Ascitic fluid levels of the following 17 cytokines were determined before and after NCT: IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, INF-γ, MCP-1 (MCAF), MIP-1, and TNF-α.

Study Results: In the group of patients who completed the study (n = 17) post-NCT levels of all cytokines were significantly lower (р ≤ 0.05), with reduction in IL-6 and IL-8 levels being particularly marked: from 3,799.7 ± 177.8 to 619.6 ± 36.8 ng/mL and from 116.4 ± 6.5 to 52.5 ± 3.2 ng/mL, respectively. The patient with an unfavorable prognosis and poor response to NCT demonstrated initially high levels of IL-5, IL-6, IL-10, and MCP-1 (MCAF). After NCT there were no positive changes, i.e. no reduction in the levels of IL-1β, IL-4, IL-5, IL-6, IL-8, IL-17, G-CSF, IFN-γ, MCP-1 (MCAF), or TNF-α in the ascitic fluid. Her IL-10 level rose. Thus, no reduction in cytokine levels may be a predictor of an unfavorable prognosis.

In the subgroup of patients withdrawn from the main group, the following data are of interest. Women with ovarian cystadenoma had the lowest levels of IL-6 (113 ng/mL), IL-10 (3.3 ng/mL), IL-1β (0.6 ng/mL), IL-4 (1.2 ng/mL), G-CSF (1.99 ng/mL), IFN-γ (15.9 ng/mL), and TNF-α (17.4 ng/mL). The patient with a granulosa cell tumor had the lowest levels of IL-1β (0.5 ng/mL), IL-4 (0.2 ng/mL), IL-6 (375.4 ng/mL), IL-8 (18.7 ng/mL), IL-10 (3.5 ng/mL), and IFN-γ (7.5 ng/mL); and undetectable levels of G-CSF. The patient who had not undergone NCT had high levels of the following cytokines in her intraoperatively obtained samples of ascites fluid: IL-1β (5.1 ng/mL), IL-4 (4.6 ng/mL), IL-6 (9,728.7 ng/mL), IL-8 (368.7 ng/mL), G-CSF (12.1 ng/mL), MCP-1 (MCAF) (227.2 ng/mL), TNF-α (87.9 ng/mL), and IFN-γ (86.3 ng/mL), which significantly exceeded those in the group of patients who had undergone NCT.

Conclusion: In patients with OC cytokine levels in the ascitic fluid may be considered biomarkers required for a timely assessment of the tumor susceptibility to certain drugs and/or treatment changes.

O. I. Aleshikova — Russian Scientific Centre for Radiology, Moscow. E-mail:

I. B. Antonova — Russian Scientific Centre for Radiology, Moscow. E-mail:

N. A. Babaeva — Russian Scientific Centre for Radiology, Moscow. E-mail:

Е. V. Gerfanova — Academician V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatalology, Moscow. E-mail:

V. O. Shender — Federal Scientific and Clinical Center of Physical and Chemical Medicine, Moscow. Academicians M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Moscow. E-mail:

L. A. Ashrafyan — Academician V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatalology, Moscow. E-mail:

20 February 14:44
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