Russian Cancer Research Center

Russian, Russia

Russian Cancer Research Center

Russian, Russia
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Jagiello-Gruszfeld A.,Nzoz Onko Med | Tjulandin S.,Russian Cancer Research Center | Manikhas A.,St. Petersburg City Oncological Dispensary | Pienkowski T.,Centrum Onkologii Instytut im Marii Sklodowskiej Curie | And 3 more authors.
Oncology | Year: 2010

Introduction: Lapatinib, an orally active tyrosine kinase inhibitor of epidermal growth factor receptor ErbB1 (EGFR) and ErbB2 (HER2), has activity as monotherapy and in combination with chemotherapy in HER2-overexpressing metastatic breast cancer (MBC). Methods: This phase II single-arm trial assessed the safety and efficacy of first-line lapatinib in combination with paclitaxel in previously untreated patients with HER2-overexpressing MBC. The primary endpoint was the overall response rate (ORR). Secondary endpoints were the duration of response (DoR), time to response, time to progression, progression-free survival (PFS), overall survival, and the incidence and severity of adverse events. All endpoints were investigator- and independent review committee (IRC)-assessed. Results: The IRC-assessed ORR was 51% (29/57 patients with complete or partial response) while the investigator-assessed ORR was 77% (44/57). As per the IRC, the median DoR was 39.7 weeks, and the median PFS was 47.9 weeks. The most common toxicities were diarrhea (56%), neutropenia (44%), rash (40%), fatigue (25%), and peripheral sensory neuropathy (25%). Conclusions: First-line lapatinib plus paclitaxel for HER2-overexpressing MBC produced an encouraging ORR with manageable toxicities. This combination may be useful in first-line treatment for patients with HER2-overexpressing MBC and supports the ongoing evaluation of this combination as first-line therapy in HER2-overexpressing MBC. Copyright © 2010 S. Karger AG, Basel.

Fuchs C.S.,Dana-Farber Cancer Institute | Azevedo S.,Hospital Of Clinicas Of Porto Alegre | Okusaka T.,National Cancer Center Hospital | Van Laethem J.-L.,Erasme University Hospital | And 18 more authors.
Annals of Oncology | Year: 2015

Background: This double-blind, phase 3 study assessed the efficacy and safety of ganitumab combined with gemcitabine as first-line treatment of metastatic pancreatic cancer. Patients and methods: Patients with previously untreated metastatic pancreatic adenocarcinoma were randomly assigned 2: 2: 1 to receive intravenous gemcitabine 1000 mg/m2 (days 1, 8, and 15 of each 28-day cycle) plus placebo, ganitumab 12 mg/kg, or ganitumab 20 mg/kg (days 1 and 15 of each cycle). The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), safety, and efficacy by levels of circulating biomarkers. Results: Overall, 322 patients were randomly assigned to placebo, 318 to ganitumab 12 mg/kg, and 160 to ganitumab 20 mg/kg. The study was stopped based on results from a preplanned futility analysis; the final results are reported. Median OS was 7.2 months [95% confidence interval (CI), 6.3-8.2] in the placebo arm, 7.0 months (95%CI, 6.2-8.5) in the ganitumab 12-mg/kg arm [hazard ratio (HR), 1.00; 95% CI, 0.82-1.21; P = 0.494], and 7.1 months (95% CI, 6.4-8.5) in the ganitumab 20-mg/kg arm (HR, 0.97; 95% CI, 0.76-1.23; P = 0.397). Median PFS was 3.7, 3.6 (HR, 1.00; 95% CI, 0.84-1.20; P = 0.520), and 3.7 months (HR, 0.97; 95% CI, 0.77-1.22; P = 0.403), respectively. No unexpected toxicity was observed with ganitumab plus gemcitabine. The circulating biomarkers assessed [insulin-like growth factor-1 (IGF-1), IGF-binding protein-2, and -3] were not associated with a treatment effect on OS or PFS by ganitumab. Conclusion: Ganitumab combined with gemcitabine had manageable toxicity but did not improve OS, compared with gemcitabine alone in unselected patients with metastatic pancreatic cancer. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Poveda A.,Valencian Institute of Oncology | Vergote I.,University Hospital | Tjulandin S.,Russian Cancer Research Center | Kong B.,Shandong University | And 9 more authors.
Annals of Oncology | Year: 2011

Background: OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD) over PLD alone in relapsed ovarian cancer. The optimal management of patients with partially platinum-sensitive relapse [6-12 months platinum-free interval (PFI)] is unclear. Patients and methods: Within OVA-301, we therefore now report on the outcomes for the 214 cases in this subgroup. Results: Trabectedin/PLD resulted in a 35% risk reduction of disease progression (DP) or death [hazard ratio (HR) = 0.65, 95% confidence interval (CI), 0.45-0.92; P = 0.0152; median progression-free survival (PFS) 7.4 versus 5.5 months], and a significant 41% decrease in the risk of death (HR = 0.59; 95% CI, 0.43-0.82; P = 0.0015; median survival 23.0 versus 17.1 months). The safety of trabectedin/PLD in this subset mimicked that of the overall population. Similar proportions of patients received subsequent therapy in each arm (76% versus 77%), although patients in the trabectedin/PLD arm had a slightly lower proportion of further platinum (49% versus 55%). Importantly, patients in the trabectedin/PLD arm survived significantly longer after subsequent platinum (HR = 0.63; P = 0.0357; median 13.3 versus 9.8 months). Conclusion: This hypothesis-generating analysis demonstrates that superior benefits with trabectedin/PLD in terms of PFS and survival in the overall population appear particularly enhanced in patients with partially sensitive disease (PFI 6-12 months). © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Reck M.,Krankenhaus Grosshansdorf | von Pawel J.,Pneumology Clinic | Zatloukal P.,Charles University | Ramlau R.,Regional Center for Lung Disease | And 7 more authors.
Annals of Oncology | Year: 2010

Background: Bevacizumab, the anti-vascular endothelial growth factor agent, provides clinical benefit when combined with platinum-based chemotherapy in first-line advanced non-small-cell lung cancer. We report the final overall survival (OS) analysis from the phase III AVAiL trial. Patients and methods: Patients (n = 1043) received cisplatin 80 mg/m2 and gemcitabine 1250 mg/m2 for up to six cycles plus bevacizumab 7.5 mg/kg (n = 345), bevacizumab 15 mg/kg (n = 351) or placebo (n = 347) every 3 weeks until progression. Primary end point was progression-free survival (PFS); OS was a secondary end point. Results: Significant PFS prolongation with bevacizumab compared with placebo was maintained with longer follow-up {hazard ratio (HR) [95% confidence interval (CI)] 0.75 (0.64-0.87), P = 0.0003 and 0.85 (0.73-1.00), P = 0.0456} for the 7.5 and 15 mg/kg groups, respectively. Median OS was >13 months in all treatment groups; nevertheless, OS was not significantly increased with bevacizumab [HR (95% CI) 0.93 (0.78-1.11), P = 0.420 and 1.03 (0.86-1.23), P = 0.761] for the 7.5 and 15 mg/kg groups, respectively, versus placebo. Most patients (∼62%) received multiple lines of poststudy treatment. Updated safety results are consistent with those previously reported. Conclusions: Final analysis of AVAiL confirms the efficacy of bevacizumab when combined with cisplatin-gemcitabine. The PFS benefit did not translate into a significant OS benefit, possibly due to high use of efficacious second-line therapies. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

PubMed | Russian Cancer Research Center
Type: Journal Article | Journal: Cancer biology & medicine | Year: 2016

Sarcoidosis is a benign systematic granulomatous disorder of unknown etiology and is associated with various malignancies. However, granulomatous and metastatic lymph node lesions are difficult to distinguish even when using precise and modern diagnostic methods, such as positron emission tomography. Thus, histological verification is the only method that can be used to accurately describe the nature of this disease. In this article, we report a case of non-luminal HER-2/neu-positive breast cancer in a patient without history of sarcoidosis and suspected to have metastatic disease.

PubMed | Karolinska Institutet, Harvard University, Ontario Cancer Institute, Russian Cancer Research Center and 18 more.
Type: Journal Article | Journal: Carcinogenesis | Year: 2016

Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.7310(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.6410(-6)), rs112290073 (OR = 1.85, P = 1.2710(-5)), rs138895564 (OR = 2.16, P = 2.0610(-5); among young cases, OR = 3.77, P = 8.4110(-4)). In addition, we found that rs139852726 (P = 1.4410(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.8410(-7)) and lung cancer (P = 2.3710(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.

Waller C.F.,Medizinische Universitatsklinik | Semiglazov V.F.,Nn Petrov Research Institute Of Oncology | Tjulandin S.,Russian Cancer Research Center | Bentsion D.,Sverdlovsk Regional Oncology Center | And 2 more authors.
Onkologie | Year: 2010

Background: Filgrastim was developed to treat chemotherapy-induced neutropenia. This phase III study was designed to demonstrate bioequivalence of Amgen filgrastim and a biosimilar filgrastim developed by Hospira (Study GCF071; sponsored by Hospira). Patients and Methods: Breast cancer patients suitable for treatment with doxorubicin and docetaxel in the neoadjuvant/adjuvant or first-line metastatic setting were enrolled at 37 European centers. Patients were randomized (2:1) to receive Hospira filgrastim or Amgen filgrastim, after the end of chemotherapy. Filgrastim (5 μg/kg/day) was administered under double-blind conditions. Primary endpoint to demonstrate bioequivalence was duration of severe neutropenia (DSN) in cycle 1. Results: 184 patients were randomized to Hospira filgrastim and 95 to Amgen filgrastim. Mean DSN in cycle 1 was similar with Hospira filgrastim (1.6 days; n = 165) and Amgen filgrastim (1.3 days; n = 85), meeting predefined criteria for bioequivalence. Secondary endpoints supporting bioequivalence included mean time to absolute neutrophil count recovery and incidence of febrile neutropenia. The most common treatment-related adverse event with Hospira filgrastim was grade 1-2 bone pain. Conclusions: Hospira filgrastim and Amgen filgrastim are bioequivalent in efficacy with similar safety profiles. Hospira filgrastim may be useful for the prophylaxis of complications related to neutropenia caused by chemotherapy. © 2010 S. Karger AG, Basel.

Iveson T.,University of Southampton | Donehower R.C.,Johns Hopkins Cancer Center | Davidenko I.,State Institution of Public Health Regional Clinical Oncology Dispensary | Tjulandin S.,Russian Cancer Research Center | And 12 more authors.
The Lancet Oncology | Year: 2014

Background: Dysregulation of the hepatocyte growth factor (HGF)/MET pathway promotes tumour growth and metastasis. Rilotumumab is a fully human, monoclonal antibody that neutralises HGF. We aimed to assess the safety, efficacy, biomarkers, and pharmacokinetics of rilotumumab combined with epirubicin, cisplatin, and capecitabine (ECX) in patients with advanced gastric or oesophagogastric junction cancer. Methods: We recruited patients (≥18 years old) with unresectable locally advanced or metastatic gastric or oesophagogastric junction adenocarcinoma, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, who had not received previous systemic therapy, from 43 sites worldwide. Phase 1b was an open-label, dose de-escalation study to identify a safe dose of rilotumumab (initial dose 15 mg/kg intravenously on day 1) plus ECX (epirubicin 50 mg/m2 intravenously on day 1, cisplatin 60 mg/m2 intravenously on day 1, capecitabine 625 mg/m2 twice a day orally on days 1-21, respectively), administered every 3 weeks. The phase 1b primary endpoint was the incidence of dose-limiting toxicities in all phase 1b patients who received at least one dose of rilotumumab and completed the dose-limiting toxicity assessment window (first cycle of therapy). Phase 2 was a double-blind study that randomly assigned patients (1:1:1) using an interactive voice response system to receive rilotumumab 15 mg/kg, rilotumumab 7·5 mg/kg, or placebo, plus ECX (doses as above), stratified by ECOG performance status and disease extent. The phase 2 primary endpoint was progression-free survival (PFS), analysed by intention to treat. The study is registered with, number NCT00719550. Findings: Seven of the nine patients enrolled in the phase 1b study received at least one dose of rilotumumab 15 mg/kg, only two of whom had three dose-limiting toxicities: palmar-plantar erythrodysesthesia, cerebral ischaemia, and deep-vein thrombosis. In phase 2, 121 patients were randomly assigned (40 to rilotumumab 15 mg/kg; 42 to rilotumumab 7·5 mg/kg; 39 to placebo). Median PFS was 5·1 months (95% CI 2·9-7·0) in the rilotumumab 15 mg/kg group, 6·8 months (4·5-7·5) in the rilotumumab 7·5 mg/kg group, 5·7 months (4·5-7·0) in both rilotumumab groups combined, and 4·2 months (2·9-4·9) in the placebo group. The hazard ratio for PFS events compared with placebo was 0·69 (80% CI 0·49-0·97; p=0·164) for rilotumumab 15 mg/kg, 0·53 (80% CI 0·38-0·73; p=0·009) for rilotumumab 7·5 mg/kg, and 0·60 (80% CI 0·45-0·79; p=0·016) for combined rilotumumab. Any grade adverse events more common in the combined rilotumumab group than in the placebo group included haematological adverse events (neutropenia in 44 [54%] of 81 patients vs 13 [33%] of 39 patients; anaemia in 32 [40%] vs 11 [28%]; and thrombocytopenia in nine [11%] vs none), peripheral oedema (22 [27%] vs three [8%]), and venous thromboembolism (16 [20%] vs five [13%]). Grade 3-4 adverse events more common with rilotumumab included neutropenia (36 [44%] vs 11 [28%]) and venous thromboembolism (16 [20%] vs four [10%]). Serious adverse events were balanced between groups except for anaemia, which occurred more frequently in the combined rilotumumab group (ten [12%] vs none). Interpretation: Rilotumumab plus ECX had no unexpected safety signals and showed greater activity than placebo plus ECX. A phase 3 study of the combination in MET-positive gastric and oesophagogastric junction cancer is in progress. © 2014 Elsevier Ltd.

Vergier B.,Bordeaux University Hospital Center | Prochazkova-Carlotti M.,Bordeaux University Hospital Center | De La Fouchardiere A.,Center Leon Berard | Cerroni L.,Medical University of Graz | And 8 more authors.
Modern Pathology | Year: 2011

Some melanocytic tumors are ambiguous, so the reproducible histopathological diagnosis of benign or malignant lesion is difficult. This study evaluated the contribution of fluorescence in situ hybridization (FISH) first in 43 non-equivocal melanomas and nevi, and then in 113 ambiguous melanocytic tumors selected by expert pathologists from six different European institutions. We included two groups of ambiguous tumors: patients without recurrence (5-year minimal follow-up) and with metastases. An independent triple-blind histopathological review was performed to classify tumors as favor benign (A) or favor malignant (A). A four-color probe set targeting 6p25, 6q23, 11q13 and CEP6 was used for FISH. In the 43 non-equivocal melanomas and nevi, sensitivity was 85% and specificity 90%. Ninety out of 95 ambiguous melanocytic tumors included were FISH interpretable (67 FISH negative and 23 FISH positive). Of the 90 patients, 69 presented no recurrence and 21/90 exhibited metastases. These ambiguous tumors were mostly spitzoid tumors (45/90). Histopathological reviewers classified these tumors as favor malignant (49/90) and favor benign (32/90), whereas nine cases had a discordant diagnosis. By comparison with outcome, the sensitivity and specificity of histopathological review were 95 and 52%, and the sensitivity and specificity of FISH were 43 and 80%. Compared with histopathological review, the sensitivity and specificity of FISH were 34.5 and 91%. Interestingly, by combining the histopathological diagnosis with FISH results, the diagnosis was optimized, especially by increasing specificity (76% instead of 52% for expert diagnosis alone) and by improving sensitivity compared with FISH alone (90 vs 43% for FISH result alone). The value of this FISH test is to add a reproducible demonstration of malignancy to the histopathological diagnosis, especially in doubtful/ambiguous melanocytic tumors. A positive FISH test reinforces the diagnosis of melanoma, allowing such tumors (particularly thick tumors) to be managed as melanomas. © 2011 USCAP, Inc. All rights reserved.

PubMed | Russian Cancer Research Center
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

1033 Background: The existing methods of forecasting of malignancies and forming o of increased oncological risk groups are unserviceable for practical use because of their low reliability (no more than 84%).There was elaborated an original method for forming of increased oncological risk groups with reliability of 95%. It is based on factor analysis, including the data of phenotypes and genotypes, anamnesis, laboratory testing with further computer processing. The result lies in determination of a factor number. Its quantity forms figures of oncological risk rate. The dependence of risk rate on the quantity of a factor number is ascertained on the basis of data of more than 10000 observations ( table ). The patients with risk rate more than 80-90% are subjected to complex examination according to the elaborated algorithms. In case of absence of clinical symptoms of this or that organ lesion, each-organ search is being made in order to detect malignant neoplasms in accordance with their frequency on the territory of Altai region.There were examined 4775 patients who happened to be in the zone of radioactive influence of Semipalatinsk nuclear testing ground (aged 43 years - 83 years old): male - 1639, female - 3136. 191 (4.0%) cases of cancer were detected: thyroid gland cancer - 56 cases, mammary gland cancer - 23, skin cancer - 49, uterine cervix cancer - 14, stomach cancer -11, lungs cancer -11, others -27. 5 cases of cancer in situ were revealed. Specific gravity of early forms of cancer was 96.5%.The research proved high effectiveness of the elaborated method for increased oncological risk group formation. [Table: see text] No significant financial relationships to disclose.

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