Malignant ascites is a common manifestation of advanced cancers, and treatment options are limited. The trifunctional antibody catumaxomab (anti-epithelial cell-adhesion molecule x anti-CD3) represents a targeted immunotherapy for the intraperitoneal (i.p.) treatment of malignant ascites secondary to epithelial cancers. In this phase II/III trial (EudraCT 2004-000723-15; NCT00836654), cancer patients (n = 258) with recurrent symptomatic malignant ascites resistant to conventional chemotherapy were randomized to paracentesis plus catumaxomab (catumaxomab) or paracentesis alone (control) and stratified by cancer type (129 ovarian and 129 nonovarian). Catumaxomab was administered as an i.p. infusion on Days 0, 3, 7 and 10 at doses of 10, 20, 50 and 150 μg, respectively. The primary efficacy endpoint was puncture-free survival. Secondary efficacy parameters included time to next paracentesis, ascites signs and symptoms and overall survival (OS). Puncture-free survival was significantly longer in the catumaxomab group (median 46 days) than the control group (median 11 days) (hazard ratio = 0.254: p < 0.0001) as was median time to next paracentesis (77 versus 13 days; p < 0.0001). In addition, catumaxomab patients had fewer signs and symptoms of ascites than control patients. OS showed a positive trend for the catumaxomab group and, in a prospectively planned analysis, was significantly prolonged in patients with gastric cancer (n = 66; 71 versus 44 days; p = 0.0313). Although adverse events associated with catumaxomab were frequent, they were manageable, generally reversible and mainly related to its immunologic mode of action. Catumaxomab showed a clear clinical benefit in patients with malignant ascites secondary to epithelial cancers, especially gastric cancer, with an acceptable safety profile.

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Study of the toxicity and pharmacokinetics of free and liposomal forms of cytostatics revealed an appreciable decrease of the toxicity of high drug doses and prolongation of drug action in liposomes. The distribution of drugs in organs and tissues is shown.

Identification and characterization of the population of cancer stem cells (CSC) depends on several cellular markers, which combination is specific for the phenotype of CSC in the corresponding tumor. Several markers of CSC have already been identified in breast cancer (BC), but there are no universal indicators that could specifically identify the CSC in BC. Aims: To determine the validation of the CSC model for cell surface markers such as CD44 and CD24 and their clinical significance. Materials and Methods: Primary tumor samples of 45 patients with invasive BC without chemotherapy prior to surgery exposure were examined in paraffin blocks. CD44 and CD24 antigens expression was evaluated by the percentage of positive cells using different chromogens and the MultiVision detection system by immunohistochemical method. In this research the evaluation was determined by the following criteria: (-), negative — expression in < 10% of tumor cells; (+), positive — expression in ≥10% of cells. The same scoring system was applied for the expression of CD44+/CD24−. Results: 62.2% of investigated patients are patients older than 50 years and most of them with stage II of disease (71.0%) and luminal tumor subtypes (68.9%). We analysed the expression of CD44, CD24 and CD44+/CD24− for different patients with dividing them into two groups. The group A consists of patients with unfavorable prognosis (relapses and metastases have occurred in the first three years after diagnosis), and the group B — with a favourable prognosis (the development of metastases after three years). Median disease-free survival in the group A is 19 months, in the group B — 46 months. The difference between the overall survival (OS) curves in the groups A and B is statistically significant (p < 0.001), the risk of death was higher in the group A (hazard ratio (HR) 5.9; confidence interval (CI) 2.3–15.2). The content of CD44 cells did not differ statistically between groups A and B (p = 0.18), but there was a tendency for increasing in OS with the existence of CD44+ cells (p = 0.056). The distribution of the expression of CD24 marker did not differ between the groups (p = 0.36) as well as the OS curves (p = 0.59). Analysis of the expression of CD44+/CD24− which were considered as possible CSC, revealed a paradoxical increase (p = 0.03) of the frequency in patients of the group B (40.9%) compared to the group A (8.7%). Nevertheless, the comparison of the clinical outcomes did not reveal a statistically significant difference in the survival curves in the groups with existence and absence of CD44+/CD24– expression (p = 0.08). The analysis showed the increasing of the risk of worse clinical outcomes in the cases of expression absence of CD44+/CD24− (HR 2.8; CI 1.1–6.8). Conclusions: As a result of our research, the analysis of the quantity of assumed stem cells of the BC, which were identified by immunohistochemistry as CD44 and CD24 cells, failed to detect a statistically significant relation between groups of patients with different prognosis, and the identification of their expression is not enough for the characteristics of CSC. The obtained data demonstrating the worst clinical outcome in the cases of absence of CD44+/CD24− expression apparently require further investigations and the validation of the immunohistochemical method with the determination of the cut-off line in defining of CD44 and CD24 status.