Vol 17, No 2 (2015)

Новый препарат компании «Рош» Газива® (обинутузумаб) для терапии ранее не леченных пациентов станет доступен на российском рынке с сентября 2015 г.

Gastrointestinal stromal tumors (GISTs) were discussed within the framework of educational sections, as well as within the discussions holding on special communications after oral and poster papers, at the 2015 American Society of Clinical Oncology ASCO Annual Meeting in June, in Chicago.The most interesting studies were devoted to estimating efficiency and the optimal duration of imatinib adjuvant therapy in patients at high risk for disease progression and finding effective new drugs to treat patients with GISTs, which had resistance to traditional tyrosine kinase inhibitors.In the section of estimating efficiency of imatinib adjuvant therapy the most interesting studies were presented by H.Joensuu, - the second planned analysis of the randomized SSGXVIII/AIO trial, and C.Raut - the results of non-randomized 3-year patients observation study (PERSIST-5) concerning the efficiency of imatinib adjuvant treatment during 5 years in patients with high-risk disease development. In the second section of most interest was the oral report of the J.-Y.Blay - the results of multicenter randomized study - PAZOGIST, phase II, associated with the efficacy of pazopanib, as well as the study of Ping Chi devoted to estimating efficiency of the combination of MEK inhibitors (binimetinib) and KIT (imatinib) and M.Heinrich devoted to estimating efficiency of ponatinib in patients with GISTs, which had resistance to traditional tyrosine kinase inhibitors.

Neurofibromatosis type 1 - NF1 (Recklinghausen's disease) is one of the most common hereditary tumor syndromes. The disease is caused by mutations in the NF1 gene, which is the tumor suppressor gene and the outcome of these mutations is the rapid uncontrolled growth of cells, as well as the high possibility of malignant tumors development, including gastrointestinal stromal tumors (GISTs). NF-1- associated GISTs are characterized by wild type for c-KIT and PDGFR-α mutations (WT-wild type) and as a rule have poor tyrosine kinase inhibitors treatment response, clinically occur asymptomatically, and characterize by low mitotic activity and better prognosis. The frequency of intraabdominal NF1 is 5-25%. Not more than 5% of all cases of intraabdominal NF1 have symptoms, which greatly affect the frequency of their determination. The most frequent clinical symptoms of the GISTs associated with NF1 are gastrointestinal bleeding and duodenal ileus. This article describes the clinical characteristics of GISTs in patient with NF1 who have been underwent gastro-pancreaticoduodenal resection, because of duodenal GISTs. The described case study confirms the high efficiency of surgical treatment and better prognosis in patients with duodenal GISTs associated with neuroendocrine tumor and NF1.

This article dials with the new opportunities for the treatment of HER2-positive breast cancer with the involvement of the central nervous system (CNS). In CEREBEL study was shown that trastuzumab was not inferior to lapatinib concerning the reduction the incidence of brain metastases and had statistically significant progression-free survival advantages. The new strategy of the 1st-line therapy in disseminated HER2-positive breast cancer is to apply dual receptor blockade using two monoclonal antibodies (trastuzumab + pertuzumab) in combination with taxanes. This approach has been highly effective, even in the patients with the involvement of the CNS: the addition of pertuzumab into the combination of trastuzumab + docetaxel has increased the median time to development of CNS metastases as first site of disease progression from 11,9 to 15 months, and median overall survival - from 26,3 to 34,4 months. On the progression of HER2-positive metastatic breast cancer after usage of trastuzumab and taxanes, the advantage of new drug - T-DM1 was proven over the combination of lapatinib and capecitabin, even in the patients with brain metastases: the advantage of median overall survival in these patients was reached 13,9 months.

Objectives: to compare safety and efficacy of a single dose of empegfilgrastim and daily dosing of filgrastim for prevention of neutropenia in patients receiving AT (docetaxel 75 mg/m2 + doxorubicin 50 mg/m2). Methods. 135 patients with breast cancer were randomly assigned at a ratio of 1:1:1 to receive either single s.c. injection of empegfilgrastim at doses of 6 mg or 7.5 mg, or daily s.c. injections of filgrastim at a dose of 5 mcg/kg (until ANC≥10×109/L), 24 h after chemotherapy. The primary efficacy endpoint was the duration of grade 4 neutropenia (ANC<0.5×109/L) during the first chemotherapy cycle.Results. Mean duration of grade 4 neutropenia was significantly shorter in both groups of empegfilgrastim compared to filgrastim group: 0.905 d (6 mg), 0.791 d (7,5 mg) and 1,725 d, correspondingly. Mean difference in duration of grade 4 neutropenia between filgrastim and empegfilgrastim 7.5 mg groups was -0.934 d (95% CI -1.504 to -0.364 days); p<0.05. During the next 3 cycles of chemotherapy mean duration of grade 4 neutropenia was also significantly shorter in both groups of empegfilgrastim. A statistically significant difference when comparing the rate of severe neutropenia during the study between both groups of empegfilgrastim (6 mg - 95.24%, 7.5 mg - 79.07%) and filgrastim (100.0%) was not observed (p>0.05). Febrile neutropenia was reported in 2.38% (6 mg), 6.98% (7.5 mg) and 5.00% (filgrastim) of patients. Results of this study indicate non-inferior efficacy of empegfilgrastim compared to filgrastim, efficacy parameters were preferable in the group of 7.5 mg empegfilgrastim.

Clinical case shows hard-relapsing course, which are characterized by malignant giant cell tumor of soft tissues, even if you have a low potential for malignancy and in the absence of distant metastasis.

Doripenem is a new carbapenems antibiotic and takes an important place in the treatment of severe nosocomial infections, as well as in case of infections caused by multi-drug resistant microorganisms; and can be used for the treatment of complicated intraabdominal infection, complicated urinary tract infections (including bacteraemia), nosocomial pneumonia, including ventilator-associated pneumonia. The review presents the data of international studies concerning the determining the susceptibility of microorganisms to doripenem in vitro, including Pseudomonas aeruginosa, Acinetobacter and others, the results of pharmacokinetic and clinical studies with the drug. We discuss the approaches to overcome the microorganism resistance using prolonged infusion of doripenem, as well as antibiotic tolerance and pharmacoeconomic data.