Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial
Bang Y.-J.,Seoul National University |
Van Cutsem E.,University Hospital Gasthuisberg |
Feyereislova A.,Hoffmann-La Roche |
Chung H.C.,Yonsei University |
And 12 more authors.
The Lancet | Year: 2010
Background Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2; also known as ERBB2), was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer. Methods ToGA (Trastuzumab for Gastric Cancer) was an open-label, international, phase 3, randomised controlled trial undertaken in 122 centres in 24 countries. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation. Participants were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab. Allocation was by block randomisation stratified by Eastern Cooperative Oncology Group performance status, chemotherapy regimen, extent of disease, primary cancer site, and measurability of disease, implemented with a central interactive voice recognition system. The primary endpoint was overall survival in all randomised patients who received study medication at least once. This trial is registered with ClinicalTrials.gov, number NCT01041404. Findings 594 patients were randomly assigned to study treatment (trastuzumab plus chemotherapy, n=298; chemotherapy alone, n=296), of whom 584 were included in the primary analysis (n=294; n=290). Median follow-up was 18·6 months (IQR 11-25) in the trastuzumab plus chemotherapy group and 17·1 months (9-25) in the chemotherapy alone group. Median overall survival was 13·8 months (95 CI 12-16) in those assigned to trastuzumab plus chemotherapy compared with 11·1 months (10-13) in those assigned to chemotherapy alone (hazard ratio 0·74; 95 CI 0·60-0·91; p=0·0046). The most common adverse events in both groups were nausea (trastuzumab plus chemotherapy, 197  vs chemotherapy alone, 184 ), vomiting (147  vs 134 ), and neutropenia (157  vs 165 ). Rates of overall grade 3 or 4 adverse events (201  vs 198 ) and cardiac adverse events (17  vs 18 ) did not differ between groups. Interpretaion Trastuzumab in combination with chemotherapy can be considered as a new standard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer. Funding F Hoffmann-La Roche. © 2010 Elsevier Ltd.
Heiss M.M.,Witten/Herdecke University |
Murawa P.,Wielkoposka Cancer Center |
Koralewski P.,Rydygier Memorial Hospital |
Kutarska E.,Center of Oncology of Poland |
And 16 more authors.
International Journal of Cancer | Year: 2010
Malignant ascites is a common manifestation of advanced cancers, and treatment options are limited. The trifunctional antibody catumaxomab (anti-epithelial cell-adhesion molecule x anti-CD3) represents a targeted immunotherapy for the intraperitoneal (i.p.) treatment of malignant ascites secondary to epithelial cancers. In this phase II/III trial (EudraCT 2004-000723-15; NCT00836654), cancer patients (n = 258) with recurrent symptomatic malignant ascites resistant to conventional chemotherapy were randomized to paracentesis plus catumaxomab (catumaxomab) or paracentesis alone (control) and stratified by cancer type (129 ovarian and 129 nonovarian). Catumaxomab was administered as an i.p. infusion on Days 0, 3, 7 and 10 at doses of 10, 20, 50 and 150 g, respectively. The primary efficacy endpoint was puncture-free survival. Secondary efficacy parameters included time to next paracentesis, ascites signs and symptoms and overall survival (OS). Puncture-free survival was significantly longer in the catumaxomab group (median 46 days) than the control group (median 11 days) (hazard ratio = 0.254: p < 0.0001) as was median time to next paracentesis (77 versus 13 days; p < 0.0001). In addition, catumaxomab patients had fewer signs and symptoms of ascites than control patients. OS showed a positive trend for the catumaxomab group and, in a prospectively planned analysis, was significantly prolonged in patients with gastric cancer (n = 66; 71 versus 44 days; p = 0.0313). Although adverse events associated with catumaxomab were frequent, they were manageable, generally reversible and mainly related to its immunologic mode of action. Catumaxomab showed a clear clinical benefit in patients with malignant ascites secondary to epithelial cancers, especially gastric cancer, with an acceptable safety profile. © 2010 UICC.
Cherenkov V.G.,Novgorod State University |
Petrov A.B.,Regional Clinical Oncology Dispensary |
Ivanchenko O.G.,Regional Clinical Oncology Dispensary |
Chistyakova T.V.,Regional Clinical Oncology Dispensary |
And 2 more authors.
Voprosy Onkologii | Year: 2015
The dynamics is presented of the rates of virus dependent diseases, in particular cervical cancer (CC), which are directly connected with the level of organization of screening and subsequent treatment of cancer. It is shown that in conditions of insurance medicine a reduction of examination rooms and female enrollment in cytology screening is observed. As a result, over the past 5 years, CC incidence in the Novgorod region increased 1.2 times, and in Russia as a whole, the proportion of such cases in female population under 29 years since 2000 increased 4.5 times (from 2.0 % to 9 %). The urgent task of cancer control is to restore examination rooms, to overcome disagreements between government institutions and medical departments, to increase coverage of women by cytology screening by means of formation of the program of individual accounting of women.
Danilova N.V.,Moscow State University |
Andreeva Yu.Yu.,Moscow Medical Academy |
Korolev A.V.,Diagnostic Healthcare |
Vinogradov I.I.,Regional Clinical Oncology Dispensary |
And 2 more authors.
Arkhiv Patologii | Year: 2014
Objective. To study tubal morphological changes in different diseases of the female reproductive system and to assess its role in the histogenesis of ovarian cancer. Material and methods. Surgical materials from 77 patients were examined. In all cases, the uterine tubes were studied totally. According to morphological and clinical diagnoses, the materials obtained from the patients were divided into a few groups including, among other conditions, high-grade ovarian cancer, benign ovarian neoplasms, malignancies of other female reproductive organs, etc. Serous tubal intraepithelial carcinoma (STIC), tubal epithelial dysplasia, and other changes were assessed in each case. Results. In high-grade serous carcinoma (HGSC), there were precancer changes as dysplasia and STIC in the macroscopically intact uterine tubes in 30% of cases. The uterine tubes and ovaries were synchronously involved in 50% of cases. Such changes were absent in the fallopian tubes when the ovaries exhibited low-grade serous carcinoma, a borderline tumor or high-grade carcinoma of another histological form different from HGSC. In other malignancies of the female reproductive system, dysplasia and STIC were identified in 5 (10.9%) of 46 cases in the total examination of the uterine tubes. Conclusion. The findings support the tubal origin hypothesis for HGSC. The investigation clearly demonstrated the need for a total examination of the fallopian tubes not only in tumor lesions of the ovaries and other sites (corpus and cervix uteri, breast), but also during tumor-unassociated surgery.
A study of the level of vascular endothelial growth factor and basic fibroblast growth factor in combined treatment of patients with stage III non-small cell lung cancer using neoadjuvant chemotherapy and surgery
Rybas A.N.,Regional Clinical Oncology Dispensary |
Shutov V.A.,Regional Clinical Oncology Dispensary |
Rybas A.V.,Stavropol State Medical University |
Levchenko N.V.,Nnpetrov Research Institute Of Oncology |
And 3 more authors.
Voprosy Onkologii | Year: 2014
There were examined 198 patients with non-small cell lung cancer (NSCLC). The levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (BFGF) as predictors at using neoadjuvant chemotherapy in patients with NSCLC were studied. Determination of baseline levels of VEGF and BFGF were necessary to predict the combination treatment of patients with stage III NSCLC.
Glushkov A.N.,Kemerovo State University |
Polenok E.G.,Russian Academy of Sciences |
Gordeeva L.A.,Russian Academy of Sciences |
Mun S.A.,Russian Academy of Sciences |
And 4 more authors.
Medical Immunology (Russia) | Year: 2016
Some genetic polymorphisms of CYP and GST enzymes metabolizing low-molecular weight xenobiotics may represent endogenous risk factors for carcinogenesis. However, possible relationships between the enzyme activities, amounts of carcinogen adducts and synthesis of anticarcinogen antibodies in humans (including cancer patients) are still poorly studied. The purpose of this study was to identify possible associations between occurrence of antibodies against benzo[a]pyrene, and frequency of genetic polymorphisms of CYP1A1ß2A, CYP1A2ß1F, GSTT1, GSTM1 in healthy men and in lung cancer patients. Materials and methods. We have examined 203 men with non-small cell lung cancer and 267 apparently healthy donors without respiratory diseases. A non-competitive solid phase immunoassay of antibodies to benzo[a]pyrene was performed. Analysis of polymorphic loci within CYP1A1 (rs4646903), CYP1A2 (rs762551), GSTP1 (rs1695, rs1138272) was performed by means of real-time PCR using TaqMan technology. Null-alleles of GSTM1 (del), GSTT1 (del) genes were detected by multiplex PCR with real-time fluorescent assay. Results. Among the lung cancer patients, the proportion of cases with a high level of IgG antibodies to benzo[a]pyrene in carriers of GSTT1+ and GSTM1+ in conjunction with the CYP1A2ß1F C allele was significantly greater than in AA homozygotes CYP1A2ß1F. The risk of lung cancer was increased to 5.5 in carriers of CYP1A2ß1F C allele combined with GSTT1+ and GSTM1+ at high levels of IgG antibodies to benzo [a] pyrene. In healthy male donors, we have not found differences between the incidence of low and high levels of IgG anti-benzo[a]pyrene antibodies in the carriers of certain CYP1A1ß2A, CYP1A2ß1F, GSTT1 and GSTM1 genotypes. Conclusions. We have first reported a relationship between CYP1 and GST gene polymorphisms and specific immune response to chemical carcinogens in lung cancer patients. Immunoassays of IgG antibodies to benzo[a]pyrene combined with molecular biology studies of CYP1 and GST are recommended for the cancer risk assessment. © 2016, SPb RAACI.