№ 8 (2014)

High differentiated types of thyroid carcinoma (HDTC) constitute more than 90 % of cases. In 10-15 % of patients, distant metastases can be detected that extremely worse the prognosis. Radioactive iodine therapy remains the basis for this group of patients. This treatment provides good results, but only if the tumor cells have the ability to accumulate the radioactive iodine. For patients with radioiodi-nerefractory HDTC, prognosis remains very unfavorable. Standard cytotoxic chemotherapy is applicable with extremely discouraging results. Over the past years, the development of molecular biology has led to the discovery of the numerous targets in thyroid carcinoma. These targets include protooncogens BRAF and RET, VEGFR and PDGFR, associated with angiogenesis, and sodium-iodide symporter. Tyrosine kinase inhibitors are the most studied drugs in the clinical settings; the results of their evaluation allowed to introduce new targeted drugs in the treatment in this group of patients.

The article provides an overview of the new advances in drug therapy of HER2-positive breast cancer (BC), which are extremely important next stage of medical oncology. The analysis of studies evaluating the effectiveness of treatment of breast cancer is performed. The data of clinical study comparing the efficacy, safety and pharmacokinetic parameters of trastuzumab for subcutaneous and intravenous administration, as well as studies defining patients’ preferences in choosing these treatment options are presented. The article presents the results of CLEOPATRA trial evaluating the efficacy and safety of the combination of pertuzumab, trastuzumab, and docetaxel as first-line therapy of HER2-positive metastatic breast cancer. The design and methodology of international randomized, open EMILIA trial, evaluating the efficacy and safety of T-DM1 compared with a combination of lapatinib + capecitabine in the second-line treatment of metastatic HER2-positive breast cancer are described in detail.

Prostate cancer (PC) is one of the most urgent problems of modern oncology due to the high incidence worldwide. Annualy, over 900 thousand new cases of prostate cancer are registered in the world. The basic treatment for locally advanced and/or metastatic prostate cancer is hormone therapy. Androgenic deprivation allows to achieve stabilization of disease in more than 90% of patients; however, median time to progression after hormonal therapy is about 2 years old, then patients with tumor progression and persistent castration levels of testosterone are being grounded to the stage so-called castration-refractory prostate cancer (CRPC). Advanced CRPC is not only prognostically unfavorable disease: it significantly impairs the quality of life of patients. The main mechanisms of development of CRPC include intraprostatic conversion of androgens in the testosterone, and the intratumoral androgen synthesis due to increased expression of steroidogenic enzymes such as cytochrome P450S17 (CYP17). The article presents an overview of new therapies for patients with the use of 2nd line chemotherapy of CRPC with cabazitaxel, therapy with selective CYP17 inhibitor abiraterone, superselective antiandrogen enzalutamide, and vaccinotherapy with sipuleucel-T and PROSTVAC.

The article presents the results of a clinical evaluation of the effects of the mTOR inhibitor everolimus (Afinitor) in various malignancies. The drug binds an intracellular protein, leading to inhibition of mTOR-kinase activity. Additionally, it inhibits the expression of hypoxia-inducing factor and reduces the expression of epidermal growth factor (EGFR). Originally, everolimus was approved by the U.S. FDA as a drug for 2nd line treatment of advanced renal cell carcinoma. Then, he was approved for the treatment of subependymal giant cell astrocytoma associated with tuberous sclerosis, progressive neuroendocrine tumors of the pancreas, and renal angiolipomyoma as a the complex lesions in tuberous sclerosis. HR +-, HER2- metastatic breast cancer previously treated with nonsteroidal aromatase inhibitors became the latest indication for the application of everolimus (2012). The potentials for the expanding clinical use of everolimus are discussed.

The article presents the intermediate results of the evaluation of newly developed regimen of 1st line chemotherapy of metastatic colorectal cancer, including oxaliplati, irinotecan, and 5-fluorouracil in the weekly and extended mode ± panitumumab. This mode of chemotherapy has demonstrated high efficacy and low toxicity. Objective tumor response to the treatment was registered in 100 % of cases. A clinical case of the application of the three-component chemotherapy regimen for the achievement of complete tumor regression in a patient with metastatic colorectal cancer is demonstrated.

Mantle cell lymphoma (MCL) is considered as relatively rare variant of B-cell tumors with specific cytogenetic and immunophenotypic characteristics. Median patient’s age is 65 years. Currently, the only method of adequate treatment of disease is allogeneic transplantation, the possibility of which is primarily determined by the patient's age and comorbidity. Elderly age and comorbidities may preclude the most effective treatment programs, including high-dose cytarabine followed by high-dose chemotherapy and autologous hemopoietic stem cell transplantation. All this necessitates the development of individualized approaches to the treatment of elderly patients with MCL. The international randomized study shows that use of R-CHOP regimen (rituximab, doxorubicin, vincristine, cyclophosphamide, prednisolone) for the elderly patients with primary MCL followed by maintenance therapy with rituximab allows to achieve satisfactory progression-free survival. In some cases, however, the presence of concomitant diseases interferes with the use of R-CHOP regimen. Program with bendamustine in combination with rituximab can be considered as alternative a as less toxic and comparable in efficacy. Relapses of the disease are observed in absolute majority of patients with MCL. This publication presents a clinical case of successful use of bendamustine in the treatment of relapse of MCL in patient aged 80.

With the advent of trastuzumab, vector of the prognostic significance of tumor marker has been changed for the first time in oncology practice - patients with HER2-positive tumors, previously considered as the most unfavorable, currently have the best prognosis. HER2 blockade strategy has been so successful that now it is the most extensively studying direction in the treatment of breast cancer (BC). The combination of pertuzumab, trastuzumab and docetaxel as first-line therapy for metastatic breast cancer has increased the progression-free survival by 6 months, and the use of trastuzumab as a neoadjuvant therapy has allowed to achieve complete pathological remission in 63 % of cases. Trastuzumab in combination with lapatinib in patients with progression on trastuzumab-containing regimens, has allowed to increase overall survival by 4.5 months; trastuzumab in the neoadjuvant therapy in combination with paclitaxel has allowed to achieve complete pathological remission in 51 % of cases.