Introduction/Objective. The purpose of this study was to assess the effectiveness of different approaches in the treatment of metastatic melanoma in daily clinical practice in a situation with limited and late availability of new drugs in a resource-limited country and to compare these parameters with those reported in clinical studies and from other real-world data. Methods. Main methods included assessment of overall survival (OS) and progression-free survival (PFS). Patients were included in the study if they were treated with first or second-line systemic therapy for radiologically/pathologically confirmed metastatic melanoma. Patients were divided into four groups based on the type of therapy they received: chemotherapy (dacarbazin), BRAF inhibitor (vemurafenib), BRAF/MEK inhibitors (vemurafenib/cobimetinib and trametinib/dabrafenib) and anti PD-1 therapy with pembrolizumab. Results. Regardless of the line of therapy, the calculated median OS in chemotherapy and vemurafenib group was nine months. The median OS in the BRAF/MEK inhibitor group was 14 months and 15 months in the pembrolizumab group. Median PFS in the chemotherapy group was four months, seven months for vemurafenib, in the BRAF/MEK inhibitor group nine months and in the pembrolizumab group six months. There was a statistically significant difference in survival between first and second-line therapy in the pembrolizumab group. Conclusion. Our results showed lower median OS and PFS in comparison to reported data from clinical trials. Compared to other real-world data from countries with similar problems related to the late reimbursement of new drugs, our research has shown similar results.

Background / Aim. FOLFOX (5fluorouracil, folinic acid, oxaliplatin)/CapOx (capecitabine, oxaliplatin) plus bevacizumab and FOLFIRI (5 fluorouracil, folinic acid, irinotecan) plus bevacizumab are a standard treatment options for a first line treatment of metastatic colorectal carcinoma (mCRC). The aim of this study was to compare overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) in the groups of patients with mCRC who were treated in the first line with FOLFIRI/bev versus FOLFOX/bev. At the same time, it was compared the safety profile in observed groups of patients and investigated optimal treatment duration and characteristics of patients who had the best treatment outcomes. Methods. In a retrospective-prospective study, patients with mCRC were treated with a chemotherapy protocols for the first line in combination with bevacizumab (FOLFOX/bev, respectively, FOLFIRI/bev). Treatment efficacy was evaluated on the basis of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS), and the safety of treatment was evaluated by monitoring adverse drug reactions. Results. ORR was 70% in the FOLFIRI/bev group and 50% in the FOLFOX/bev group. Median PFS for FOLFIRI/bev (n = 30) and for FOLFOX/bev (n = 30) was 15.6 months and 12.1 months respectively (HR, 0.85; 95% confidence interval (CI) 0.47-1.53; P = 0.5591). Median OS for FOLFIRI/bev and for FOLFOX/bev was 24.7 months and 19.9 months respectively (HR, 0.67; 95% confidence interval (CI) 0.37-1.23; P = 0.1552). In both patient groups, the patients who received more than 9 cycles of induction therapy had better treatment response in comparison with patients who received less than 9 cycles of therapy. In FOLFOX/bev group PFS was 16.9 versus 9.7 months and OS was 22.1 versus 17.6 months respectively. In FOLFIRI/bev group PFS was 9 months for patients who received less than 9 cycles of therapy versus 18.8 months for patients who received more than 9 cycles, OS was 18.0 versus 27.7 respectively. The adverse drug reactions grade 3 and 4 were 7% in the FOLFIRI/bev group versus 27% in the FOLFOX/bev group. Conclusion. Patients who received FOLFIRI/bev had better ORR (70 % versus 50 %), PFS (15.6 versus 12.1 months) and OS (24.7 versus 19.9 months). In both patient groups, better treatment response had the patients who received induction therapy for 4-6 months (more than 9 cycles of therapy).

Doxorubicin (DOX) is one of the drugs necessary for the treatment of the 10 most common types of cancer. The leading adverse effect limiting clinical use of DOX is cardiotoxicity. Given that literature data indicate a protective role of carotenoids in doxorubicin-induced toxicity, in our study we compared the cardioprotective effect of a mixture of pumpkin carotenoids and a commercially available antioxidant preparation. Animals were distributed in 8 groups (Control -S; NADES -N; Doxorubicin -Dox; Carotenoids -Car; CardiofortIN -CF; NADES-Doxorubicin -N-Dox; Carotenoids-Doxorubicin -Car-Dox; CardiofortIN-Doxorubicin -CF-Dox). Histological sections were stained with the hematoxylin-eosin (HE) and analyzed for the presence of myocardial damage by doxorubicin damage score (DDS). From the heart tissue homogenate were determined the intensity of lipid peroxidation and specific antioxidative enzyme activity (superoxide dismutase; catalase; glutathione S-transferase; glutathione peroxidase). In Car-DOX and CF-DOX groups, lipid peroxidation is significantly reduced compared to DOX group. Pretreatment of animals with carotenoids and in lesser extent with CardiofortIN led to higher antioxidative enzymes activity, compared to DOX group. Pretreated with carotenoids, only 50 % of animals had some degree of myocardial damage, and no animals had extensive damage. CardiofortIN pretreatment showed less protective effect. Pretreatment with carotenoid extract, reduced DDS significantly, so Car-DOX group has changes equivalent to mild myocardial damage. Although CardiofortIN pretreatment lowered DDS score values, animals still had moderate level of myocardium damage. This in vivo study and its findings indicate that carotenoids extracted from pumpkin may be a promising cardioprotective agent against doxorubicin induced cardiotoxicity, at least in part mediated through inhibition of DOX-induced oxidative stress.

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Background/Aim. Brain metastases occur in 20%-30% of all patients with systemic cancer. We aimed at investigating whether patients with oligometastatic brain disease treated with whole brain radiotherapy (WBRT) and simultaneous integrated boost of brain metastases (SIBmets) improved overall survival (clinical outcomes) compared with patients from the Radiation Therapy Oncology Group (RTOG) 9508 database, treated with WBRT and sequential stereotactic radiosurgery (SRS) boost. Methods. WBRT with SIBmets, using the RapidArc (RA) (Varian Medical Systems, Palo Alto, CA) volumetric modulated arc technique (VMAT), was delivered to 15 patients with computed tomography/magnetic resonance imaging (CT/MRI) findings of 1-3 brain metastases with a diameter less than 40 mm for the largest lesion. Radiotherapy (RT) plans consisted of WBRT, with a prescribed dose of 20 Gy in 5 fractions, with SIBmets which was also 20 Gy (gray units) in 5 fractions. Results. A group of 15 patients included 8 males and 7 females with the mean age of 56.3 years. Three patients were in the RTOG Recursive Partitioning Analysis (RPA) Class I and other 12 patients in RPA Class II. Four patients had one metastasis and 11 patients had two metastases. Calculated mean survival time (MST) was 7.49 ± 4.36 months with no statistically significant difference compared to RTOG 9508 results (MST = 6.5 months) (p = 0.197). The local control rate for 7 patients after three months was 85.7%. Conclusion. WBRT with SIBmets and WBRT + SRS are clinically equivalent treatment options for the patients with oligometastatic brain disease. In comparison to the WBRT + SRS, the treatment by WBRT + SIBmets technique reduces the treatment time and improves the patient's treatment comfort.