No 17 (2016)

Angiogenesis plays a major role in the growth and progression of non-small cell lung cancer (NSCLC), and there is increasing interest in the development of therapies that block this particular aspect of tumorigenesis. Bevacizumab was the first approved inhibitor of angiogenesis after demonstrating improved progression-free survival and overall survival in combination with chemotherapy in treating NSCLC. However, the benefit of bevacizumab is only modest and transient as the tumors inevitably develop resistance to this particular treatment. Therefore, new therapies are being developed that attempt to inhibit angiogenesis through several different pathways. One promising new drug, nintedanib, is an oral triple angiokinase inhibitor that acts by blocking not only VEGFR, but also FGFR and PDGFR, which are involved in the development of resistance to bevacizumab. This article discusses the rationale for this approach and summarizes the clinical trial data on nintedanib, including the two most recent phase III trials.

The introduction of PD-1 inhibitors - nivolumab and pembrolizumab - into the second-line treatment of advanced non-small cell lung cancer (NSCLC) followed successful clinical trials of these drugs and was an important step in the development of treatment strategies in NSCLC. A new type of treatment showed a significant increase in objective response rate and overall survival and more favorable spectrum of complications compared to standard chemotherapy with docetaxel. The review discusses the features of assessment of the dynamics of disease manifestations during the treatment with inhibitors of the control points of the immune response, the specificity of drug toxicity, and issues of determining the PD-L1 expression requiring further development.

The article presents the results of the meeting of the Expert Council «Modern approaches to the treatment of HER2-negative metastatic breast cancer. Prospects for the use of eribulin as a part of combination therapy for breast cancer». The meeting was held on November 15, 2015, and discussed the modern world standards of treatment HER2-negative metastatic breast cancer (MBC); the results of clinical studies on the use of eribulin at different subtypes of breast cancer, and in combination with other drugs, as well as in other nosology, were considered; expert opinion on the prospects for the use of eribulin in a combination therapy for breast cancer based on the latest research data and clinical experience of meeting members was derived.

In order to evaluate the efficacy and toxicity of sunitinib in previously treated 19 patients with neuroendocrine tumors (NETs) of the pancreas, the safety profile with pancreatic NETs G1, G2 was assessed. Stabilization was observed in the majority (78.6%) of patients, the progression was registered in 1 (7.1%) patient. Duration of stabilization (median) was 395 days (95% CI, 162-518 days). The results showed that the efficacy of treatment with sunitinib corresponds to the results presented in the world literature. Identified adverse events correlate with the known toxicity profile of the drug.

Peritoneal carcinomatosis (PC) in stomach cancer (SC) occurs in more than 50% of patients. The median survival of patients without treatment is 3-6 months, with systemic chemotherapy (SC) - rarely more than 8-12 months. The use of pressurized intraperitoneal aerosol chemotherapy (PIAC) allows to improve the results of treatment of this difficult group of patients. According to the protocol of the clinical study, all the patients at the first stage underwent staging laparoscopy or laparotomy, 3-4 courses of systemic chemotherapy followed by 3 sessions of PIAC with an interval of 6 weeks against the background of continuing systemic chemotherapy. In the case of progression, the patient was eliminated from the study. The main criteria for progression included: increase in peritoneal cancer index (PCI) > 50%, the development of distant nodal and hematogenous metastases, lack of medical pathomorphosis according to repeated biopsies or pronounced deterioration in the general condition. The study included 37 patients (11 men, 26 women, mean age - 53.4 years), among them 26 stomach cancer patients with synchronously diagnosed PC and 11 patients with metachronously diagnosed isolated PC after previous treatment. Middle PCI was 12.9 (3 to 34) points. Total of 68 PIAC procedures were performed. Objective pathomorphological response was obtained in 87.5% of cases, including complete response in 25% of patients. Median survival was 14 months, one-year survival rate - 47.8%. Thus, a combined approach to treatment of PC in SC combining systemic chemotherapy according to the XELOX scheme and PIAC with low doses of cisplatin and doxorubicin leads to an objective regression of the tumor and increases overall survival.

The study was aimed to the development of algorithm to identify the progression of prostate cancer after radical prostatectomy (RPE). The study involved 140 patients with prostate cancer after radical prostatectomy with various degrees of risk for biochemical recurrence, which were under dispensary observation using developed algorithm in the form of monitoring the prostate-specific antigen (PSA) levels every three months. In case of biochemical recurrence with PSA>0.2 ng/mL, bone scintigraphy and magnetic resonance imaging (MRI) of the pelvis with contrast agent were performed. In the case of absence of disease foci, control of PSA levels was continued till level doubling, with subsequent repeat bone scintigraphy and MRI of the pelvis. In case of detection of locoregional or distant foci of the disease, remedial measures were carried out. The proposed algorithm of examination of patients after radical prostatectomy allows to adequate control the risk of disease progression during dispensary observation and provides a 20% reduction in the level of the cost of the examination compared to the standard observation.

Disseminated skin melanoma (DSM) is a malignant neoplasm with one of the highest mortality rates in the world. Low effectiveness of chemotherapy necessitates exploration of new groups of drugs for the treatment of DSM. The discovery of BRAF-mutation and the development of BRAF-inhibitors have significantly improved the results of treatment of the DSM, and changed the quality of life of patients. According to recent studies, the combination of targeted drugs is more effective than monotherapy. Now, combination of BRAF- and MEK-inhibitors (vemurafenib+cobimetinib) can be considered as a new standard for high effective treatment of patients with unresectable or metastatic melanoma with BRAF V600 mutation.

Pleomorphic xanthoastrocytomas are rare glial tumors. They account for less than 1% of the cerebral astrocytomas. Pleomorphic xanthoastrocytomas are low-grade glial tumors, namely, 2nd grade according to WHO classification. In some cases, however, anaplastic pleomorphic xanthoastrocytomas may develop, and they are characterized by a more aggressive course, frequent relapses, like high-grade cerebral gliomas brain (anaplastic astrocytoma or glioblastoma). BRAF V600 mutation in tumor occurs in 30-40% of cases of anaplastic pleomorphic xanthoastrocytoma. Presented clinical case demonstrates the ability to achieve long-term remission using B-raf inhibitor vemurafenib in the treatment of patient with relapses of anaplastic pleomorphic xanthoastrocytoma and with the V600E BRAF mutation in tumor. It is necessary to conduct clinical studies of BRAF inhibitors in patients with anaplastic pleomorphic xanthoastrocytomas with the presence of BRAF V600 mutations in tumor.

Metastases to the penis are extremely rare area of metastasis of malignant tumors. In the most cases the sources of metastases include prostate tumors, bladder tumors, kidney tumors, testicular tumors, colon tumors, lung tunmors, and so on. The article presents the observation of metastatic lesions of the penis in HER2-positive gastric adenocarcinoma. The patient received 3 lines of chemotherapy, none of which was effective. Short-term positive trend in the form of a reduction of pain in the penis was observed only on the background of targeted therapy with trastuzumab. The patient’s life expectancy from the initiation of treatment was 6 months. The ineffectiveness of chemotherapy in this clinical observation confirms the data of world literature about the extremely poor prognosis in patients with metastases to the penis.