Vol 17, No 3 (2015)

Терапия препаратом Варгатеф® (нинтеданиб*) в комбинации с доцетакселом способствует значительному уменьшению и замедлению роста опухоли у пациентов с аденокарциномой легкого после 1-й линии химиотерапии по сравнению с монотерапией доцетакселом. У пациентов с прогрессирующей аденокарциномой, получавших комбинированную терапию препаратами Варгатеф® и доцетаксел, в течение 6 мес лечения наблюдалось более выраженное замедление роста опухоли - на 10% медленнее по сравнению с группой, получавшей плацебо в комбинации с доцетакселом. Выраженное преимущество комбинированной терапии препаратами Варгатеф® и доцетаксел было показано у прогностически наиболее неблагоприятной группы пациентов с прогрессирующей аденокарциномой легкого

Сообщение посвящено генетическим нарушениям, возникающим и диагностируемым при меланоме.

В своем выступлении автор привела важные составляющие последних европейских и российских рекомендаций по лечению меланомы кожи.

Выступление было посвящено интерактивному разбору клинических случаев.

Краткий обзор результатов регистрационного исследования препарата Ацеллбия® - российского биоаналога ритуксимаба

Background. There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced squamous cell carcinoma of the lung. Methods. We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy. Participants were randomly assigned (1:1) to receive afatinib (40 mg per day) or erlotinib (150 mg per day) until disease progression. The randomisation was done centrally with an interactive voice or web-based response system and stratified by ethnic origin (eastern Asian vs non-eastern Asian). Clinicians and patients were not masked to treatment allocation. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). The key secondary endpoint was overall survival. This trial is registered with ClinicalTrials.gov, NCT01523587. Findings. 795 eligible patients were randomly assigned (398 to afatinib, 397 to erlotinib). Median follow-up at the time of the primary analysis of progression-free survival was 6.7 months (IQR 3.1-10.2), at which point enrolment was not complete. Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib [median 2.4 months (95% CI 1.9-2.9) vs 1.9 months (1.9-2.2); hazard ratio (HR) 0.82 (95% CI 0.68-1.00), p=0.0427]. At the time of the primary analysis of overall survival [median follow-up 18.4 months (IQR 13.8-22.4)], overall survival was significantly greater in the afatinib group than in the erloinib group [median 7.9 months (95% CI 7.2-8.7] vs 6.8 months (5.9-7.8); HR 0.81 (95% CI 0.69-0.95), p=0.0077], as were progression-free survival [median 2.6 months (95% CI 2.0-2.9) vs 1.9 months (1.9-2.1); HR 0.81 (95% CI 0.69-0.96), p=0.0103] and disease control [201 (51%) of 398 patients vs 157 (40%) of 397; p=0.0020]. The proportion of patients with an objective response did not differ significantly between groups [22 (6%) vs 11 (3%); p=0.0551]. Tumour shrinkage occurred in 103 (26%) of 398 patients versus 90 (23%) of 397 patients. Adverse event profiles were similar in each group: 224 (57%) of 392 patients in the afatinib group versus 227 (57%) of 395 in the erlotinib group had grade 3 or higher adverse events. We recorded higher incidences of treatment-related grade 3 diarrhoea with afatinib [39 (10%) vs 9 (2%)], of grade 3 stomatitis with afatinib [16 (4%) vs none], and of grade 3 rash or acne with erlotinib [23 (6%) vs 41 (10%)]. Interpretation. The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib, along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung.

Background. Hepatocellular carcinoma (HCC) is a malignancy of the liver associated with poor prognosis. The understanding of the prevalence of liver damage and functional status of the liver can complicate therapy in these patients and often requires non-standard treatment approach. In this context, the study of the results of radical liver resection, locoregional and systemic therapy for HCC remains of current interest. Materials and methods. We analyzed the experience in the treatment of HCC in 70 patients, who were treated between 1991 and 2015. We studied the main demographic characteristics, local prevalence and liver status at the beginning of therapy, the application of therapeutic methods, intraoperative data, postmanipulation complications, overall and recurrence-free survival. The paper presents the following treatment options: liver resection (n=27), transarterial chemoembolization - TACE (n=16), radiofrequency ablation - RFA (n=3) and systemic therapy (n=4), TACE + transplantation (n=6), TACE + resection (n=3), TACE + sorafenib (n=3), resection + sorafenib (n=1), resection + RFA + sorafenib (n=2), transarterial embolization + resection (n=1), resection + RFA (n=1), TACE + resection + sorafenib (n=1), RFA + TACE (n=1), transarterial embolization + sorafenib (n=1). Results. Median overall survival (OS) was 33 months in the liver resection group, 5-year survival rate was 49%, and median recurrence-free survival (RFS) was 9 month, 1-year RFS rate - 40%. Median survival of patients who underwent TACE in mono-regimen (n=16) was 9 months; 1-year survival rate was 44%, the disease relapse after radical treatment, included resection and RFA (n=40) was noted in 25 (59.5%) patients. Median RFS was 9 months in this group. OS was significantly lower in group of patients with relapse of HCC in comparison with the group without recurrences (p=0.004). Conclusions. Although we see recent advances of interventional and drug therapy in patients with HCC, surgical treatment remains a priority. Liver resection allows radically remove malignant lesion and achieve the most satisfactory results, nowadays. The combined approach is a promising direction and the studying of the efficacy of combined treatment protocols and the development of new options will help us to improve the prognosis of treatment of HCC severe categories patients.

Matrix metalloproteinase-7 (MMP-7) is able to cleave almost all the elements of the extracellular matrix. It is believed that due to its ability to degrade the basal membrane, it is involved in the processes of invasion, metastasis and neoangiogenesis. Vascular endothelium growth factor (VEGF) has demonstrated its role in tumor progression. Subjects and methods. The study included 65 patients with tumors of the ovary, 44 cancer was diagnosed. Using enzyme-linked immunosorbent assay we determined the content of MMP-7 and VEGF in the serum and tumor tissue in patients with tumors of the ovary. Results. Serum levels of MMP-7 and VEGF are positively correlated with the prevalence of ovarian cancer (OC). In the tissue of adenocarcinoma of the ovary are determined higher levels of MMP-7 and VEGF than in tissue of benign tumors. In the tumor tissue of OC registered positive correlation between VEGF and MMP-7 (r=0.6); p=0.0001. The period of observation did not exceed 2 years from the start of treatment, median follow-up time was 14 months. Only the size of residual tumor after cytoreductive surgery is significantly associated with long-term results. Communication levels of MMP-7 with long-term results of treatment of OC patients is not established. Two-year disease-free survival in patients with baseline serum VEGF value of more than 440 PG/ml was 24%, less than 440 PG/ml - 55%. Conclusions. The levels of MMP-7 and VEGF in tumor tissue and serum in patients with OC increase with the prevalence and aggressiveness of tumor process. Elevated levels of VEGF can be considered as a factor of poor prognosis in patients with OC.

Adenosquamous carcinoma of the colon is an extremely rare histological type of cancer (0.1% of all malignant neoplasms of the colon), and is characterized by a worse prognosis compared with adenocarcinoma. Here, we report a case of an adenosquamous carcinoma in a 67-year-old female, T3N0M1 (IV) stage.

This article discusses the basic mechanisms of latency some of the herpes viruses and the role of persistence of these viruses in oncogenesis. A statistically significant increase of the level of viral antibodies in patients with recurrent, locally advanced bladder cancer with high potential of malignancy; the statistically significant correlations between the presence of viral DNA cytomegalovirus and Epstein-Barr virus in the tumor and the level of antibodies, the stage of the process and recurrent nature of the tumor were found. The presence of viral DNA in the tumor was determined in 30% of cases.

The system of the insulin-like growth factors (IGF) through its mitogenic and antiapoptotic effects plays an important role in carcinogenesis. IGF with interaction with own receptor activates Ras - and Akt-signaling pathways that lead to enhanced cell proliferation and reduction of apoptosis. Via stimulation of proangiogenic factors, such as vascular endothelial growth factor (VEGF), IGF also mediates processes of neoangiogenesis that are necessary for the development, progression and metastasis of malignant tumors. Recent data show a linkage between IGF, VEGF and ovarian cancer. New drugs of targeted therapy for patients with ovarian adenocarcinoma, that inhibit the components of IGF and VEGF families, are under experimental and clinical trials. This review presents the results of investigations of IGF′ and VEGF′ role in the development, prognosis and treatment of patients with ovarian cancer.