Phase I Study of MT110 in Lung Cancer (Adenocarcinoma and Small Cell), Gastric Cancer or Adenocarcinoma of the Gastro-Esophageal Junction, Colorectal Cancer, Breast Cancer, Hormone-Refractory Prostate Cancer, and Ovarian Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Solid Tumors
PROVIDER: 2052164 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Ramucirumab, a fully humanized monoclonal antibody directed against vascular endothelial growth factor receptor 2, is the first targeted agent to have demonstrated an improvement in survival, as a single agent or in combination, in a molecularly unselected population in gastro-oesophageal cancer. Now that second-line treatment is routinely considered for patients with advanced gastro-oesophageal cancer, ramucirumab, with its favourable toxicity profile compared with cytotoxic treatment, provides a valuable additional treatment option.
| S-EPMC4622287 | biostudies-literature
Project description:Cancers of the stomach and gastro-esophageal junction represent a significant challenge in oncology. Despite some recent advances in genetic categorization and the development of novel agents, outcomes remain poor. The vascular endothelial growth factor receptor 2 monoclonal antibody ramucirumab is the first targeted therapy to improve survival in a molecularly unselected population, and represents a valuable new treatment option. This review describes the current treatment landscape for advanced disease, evaluates existing and ongoing research into ramucirumab, and discusses its current and potential future therapeutic role.
| S-EPMC4966750 | biostudies-literature
Project description:BACKGROUND AND STUDY AIMS: The HER2 status of small endoscopic biopsies is important for predicting the eligibility of patients with metastatic HER2-positive gastric cancer or gastro-esophageal junction (GEJ) cancer for anti-HER2 therapy approved by the U.S. Food and Drug Administration. The aim of this study was to identify the minimum biopsy set required to evaluate the HER2 status with confidence. PATIENTS AND METHODS: A total of 103 consecutive patients with resected gastric cancer or GEJ cancer were retrospectively selected; 2 formalin-fixed, paraffin-embedded samples of each surgical specimen and all paired endoscopic biopsies were analyzed for HER2 status with both immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) methods. A total of 10 virtual biopsies were constructed by selecting areas 2.6 mm in diameter on the luminal side of digitalized slides obtained from the surgical specimens. The results of evaluating HER2 status in virtual biopsies, slides containing complete surgical specimens, and endoscopic biopsies were compared. The resulting minimum biopsy set was applied to the endoscopic biopsy series for validation. RESULTS: A biopsy set containing a minimum of 5 samples was identified as the most accurate in predicting HER2 status (sensitivity, 92 %; specificity, 97 %). In only 3 of the 103 cases (2.9 %) did a comparison of the HER2 evaluation of virtual biopsies and that of entire slides show inconsistent results. Overall agreement between the endoscopic biopsies and surgical samples for HER2 IHC status increased from 78.4 % to 92.3 % when biopsy sets containing 4 or fewer samples were compared with biopsy sets containing 5 or more samples. CONCLUSIONS: Although the recommendations suggest that 8 to 10 biopsies are necessary, the results show that a minimum set of 5 biopsies may be sufficient for reliable HER2 assessment in gastric cancer and GEJ cancer. However, endoscopists should be aware that a smaller sample size may be less accurate in selecting patients eligible for anti-HER2 therapy.
| S-EPMC4477016 | biostudies-other
Project description:The short-term advantages of minimally invasive esophagectomy (MIE) in terms of less morbidity and better quality of life (QoL) in comparison with open esophagectomy (OE) became visible in the last few years. There are two main MIE approaches: a transthoracic esophagectomy (TTE) (either accompanied by an intrathoracic or cervical anastomosis) or a transhiatal esophagectomy (THE) (accompanied by a cervical anastomosis). Additionally, minimally invasive gastrectomy is increasingly gaining popularity over open gastrectomy. Controversy still exists about what approach is the best for esophagogastric junction tumors (EGJ) and the choice of the approach is currently based on the surgeons' discretion. In this study, we describe the definition, staging and classification, indications for each minimally invasive approach for EGJ tumors, the surgical technique, current developments and problems regarding surgical treatment for patients with cancer of the EGJ.
| S-EPMC5538974 | biostudies-other
Project description:BackgroundThe majority of cancer patients loses weight and becomes malnourished during the course of their disease. Metabolic alterations and reduced immune competence lead to wasting and an increased risk of infectious complications. In the present study, the effect of a nutritionally complete medical food, which is high in protein and leucine and enriched with fish oil and specific oligosaccharides, was investigated on immune function, nutritional status, and inflammation in patients with esophageal cancer and compared with routine care.MethodsIn this exploratory double-blind study, 64 newly diagnosed esophageal cancer patients were randomized. All patients received dietary counselling and dietary advice. In the Active group, all patients received the specific medical food for 4 weeks before the start of anticancer therapy. In the routine care control arm, patients with <5% weight loss received a non-caloric placebo product, and patients with weight loss ≥5% received an iso-caloric control product to secure blinding of the study. The required study parameters of body weight and performance status were recorded at baseline and after 4 weeks of nutritional intervention, and patients were asked to complete quality of life questionnaires. In addition, blood samples were taken for the measurement of several immune, nutritional, and safety-parameters.ResultsNo effect of the specific nutritional intervention could be detected on ex vivo stimulations of blood mononuclear cells. By contrast, body weight was significantly increased (P < 0.05) and ECOG performance status was improved after intervention with the specific medical food (P < 0.05). In addition, serum Prostaglandin E2 (PGE2) levels were significantly decreased in the specific medical food group and increased in the control group (P = 0.002).ConclusionsNutritional intervention with the specific medical food significantly increased body weight and improved performance status compared with routine care in newly diagnosed esophageal cancer patients. This effect was accompanied by significantly reduced serum PGE2 levels.
| S-EPMC4435095 | biostudies-literature
Project description:PurposeMultimodality therapy leads to improved outcomes for adenocarcinoma of the distal esophagus and gastroesophageal junction (GEJ) over surgery alone. At our institution, adjuvant chemoradiation (chemoRT) using IMRT and SIB is standard of care for resected high-risk disease. In this study, we review our experience with a recent cohort of patients treated in this manner.Methods and materialsWe identified 18 patients with resected T3 and/or N1 adenocarcinoma of the distal esophagus and GEJ who received adjuvant chemoRT. A large elective volume (PTV1) and a smaller high-risk volume (PTV2) were irradiated simultaneously using IMRT and an SIB technique. All patients received concurrent chemotherapy. Relevant clinical outcomes are reported.ResultsThe median dose to 95% of PTV1 was 3747cGy and to 95% of PTV2 was 4876cGy. All RT was given in a median of 28 daily fractions. Four patients did not complete chemotherapy. At a median follow up of 952 days from the start of RT, 7 of 18 patients were dead; of these, 3 had developed local recurrence only; 3 had developed both local and distant recurrence; 1 died of a late toxicity, without recurrence. OS was 88% at 1year, 76% at 2 years and 58% at 3 years. Freedom from local recurrence was 88% at 1 year, 82% at 2 years and 82% at 3 years. Freedom from distant recurrence was 72% at 1 year, 67% at 2 years and 56% at 3 years. Toxicity was acceptable.ConclusionsAdjuvant concurrent chemoRT with IMRT and SIB is feasible for resected high-risk adenocarcinoma of the distal esophagus and GEJ. Our results describe how modern treatment techniques can be employed as part of a treatment paradigm that is neither commonly used nor commonly described in the literature.
| S-EPMC3599957 | biostudies-literature
Project description:The high morbidity and mortality of patients with esophageal (E) and gastro-esophageal junction (GEJ) cancers, warrants new pre-clinical models for drug testing. The utility of primary tumor xenografts (PTXGs) as pre-clinical models was assessed. Clinicopathological, immunohistochemical markers (p53, p16, Ki-67, Her-2/neu and EGFR), and global mRNA abundance profiles were evaluated to determine selection biases of samples implanted or engrafted, compared with the underlying population. Nine primary E/GEJ adenocarcinoma xenograft lines were further characterized for the spectrum and stability of gene/protein expression over passages. Seven primary esophageal adenocarcinoma xenograft lines were treated with individual or combination chemotherapy. Tumors that were implanted (n=55) in NOD/SCID mice had features suggestive of more aggressive biology than tumors that were never implanted (n=32). Of those implanted, 21/55 engrafted; engraftment was associated with poorly differentiated tumors (p=0.04) and older patients (p=0.01). Expression of immunohistochemical markers were similar between patient sample and corresponding xenograft. mRNA differences observed between patient tumors and first passage xenografts were largely due to loss of human stroma in xenografts. mRNA patterns of early vs late passage xenografts and of small vs large tumors of the same passage were similar. Complete resistance was present in 2/7 xenografts while the remaining tumors showed varying degrees of sensitivity, that remained constant across passages. Because of their ability to recapitulate primary tumor characteristics during engraftment and across serial passaging, PTXGs can be useful clinical systems for assessment of drug sensitivity of human E/GEJ cancers.
| S-EPMC4380353 | biostudies-literature
Project description:BACKGROUND:TP300, a recently developed synthetic camptothecin analogue, is a highly selective topoisomerase I inhibitor. A phase I study showed good safety and tolerability. As camptothecins have proven active in oesophago-gastric adenocarcinomas, in this phase II study we assessed the efficacy and safety of TP300 in patients with gastric or gastro-oesophageal junction (GOJ) adenocarcinomas. METHODS:Eligible patients had metastatic or locally advanced gastric or Siewert Types II or III GOJ inoperable adenocarcinoma. Patients were chemotherapy naïve unless this had been administered in the perioperative setting. TP300 was administered as a 1-h intravenous infusion every 3 weeks (a cycle) for up to 6 cycles at a starting dose of 8 mg/m2 with intra-patient escalation to 10 mg/m2 from cycle 2 in the absence of dose-limiting toxicity. Tumour responses (RECIST 1.1) were assessed every 6 weeks. Toxicity was recorded by NCI-CTCAE version 3.0. Using a modified two-stage Simon design (Stage I and II), a total of 43 patients were to be included providing there were 3 of 18 patients with objective response in Stage I of the study. RESULTS:In Stage I of the study 20 patients (14 males, 6 females), median age 67 years (range 40?-?82), performance status ECOG 0/1, with GC [14] or GOJ carcinoma [6] were enrolled. Of the 16 evaluable patients, 11 received the planned dose increase to 10 mg/m2 at cycle 2, 2 decreased to 6 mg/m2, and 3 continued on 8 mg/m2. There were no objective responses after 2 cycles of treatment. Twelve patients had stable disease for 1?-?5 months and 4 had progressive disease. Median progression free survival (PFS) was 4.1 months (CI [1.6?-?4.9]), median time to progression (TTP) was 2.9 months (CI [1.4?-?4.2]). Grade 3/4 toxicities (worst grade all cycles) included 7 patients (35 %) with neutropenia, 4 patients (20 %) with anaemia, 2 patients (10 %) with thrombocytopenia, and 3 patients (15 %) with fatigue. This study was terminated at the end of Stage I due to a lack of the required (3/18) responders. CONCLUSIONS:This study of TP300 showed good drug tolerability but it failed to demonstrate sufficient efficacy as measured by radiological response. TRIAL REGISTRATION:EU-CTR 2009-012097-12 2009-09-03.
| S-EPMC5057500 | biostudies-literature
Project description:Metastatic or unresectable esophageal and gastroesophageal junction adenocarcinoma represent a devastating disease with 5-year survival rate of <5%. Although cytotoxic chemotherapy with platinum-doublet-based regimens is initially effective, patients inevitably progress. Patients often decline rapidly after this initial progression, making later lines of therapy a challenge to successfully administer There have been multiple efforts to incorporate biologic agents, targeting pathways known to be dysregulated in esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, into existing chemotherapy backbones. Other than therapeutics targeting human epidermal growth factor receptor-2 (HER2) and vascular endothelial growth factor receptor (VEGFR), other strategies have failed. Given the mixed success of biologic agents, along with the promise of immunotherapy to generate durable and sometimes complete responses, immune-agent based trials are a major area of interest for patients with this disease. Checkpoint inhibitors blocking programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have demonstrated modest single-agent efficacy in patients with progressive esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma. However, other approaches such as novel checkpoint combinations, vaccine-based approaches and autologous T cells hold more promise to change the trajectory of disease.
| S-EPMC6527138 | biostudies-literature
Project description:To delineate an optimal clinical target volume (CTV) for gastroesophageal junction (GEJ) cancers by comparing locoregional versus extended locoregional radiation (RT) volumes.This retrospective analysis examined 222 patients (111 matched pairs treated with locoregional versus extended locoregional RT) with nonmetastatic GEJ carcinomas treated with concurrent chemoradiation ± surgery. The CTV for locoregional volumes was defined as gross tumor volume + elective coverage of first-echelon nodes and sometimes the celiac axis. The CTV for extended locoregional volumes was defined as gross tumor volume + elective coverage of celiac and splenic (± porta) nodes. Variables used for matching included sex, stage, performance status, histology, receipt of induction chemotherapy, type of concurrent chemotherapy, RT modality, receipt of surgery, type of surgery, and Siewert classification. Regression models stratified by matched pairs were fit to estimate effect of RT volume on clinical endpoints.Adjusting p values for multiple testing, patients treated with extended locoregional versus locoregional RT had increased odds of grade 2+ acute chemoradiation-associated gastrointestinal toxicity (odds ratio: 2.92, adj. p = 0.0447). However, differing RT volumes were not significantly associated with postoperative complication rates, pathologic T-stage, frequency of positive perigastric/regional nodes on surgical specimen, distant-metastases progression-free survival, locoregional progression-free survival, or overall survival (adj. p > 0.05). Of the patients who did (n = 124) and did not (n = 72) receive elective celiac RT, two (1.6%) and two patients (2.8%), respectively, relapsed in the celiac nodes. No patients failed in the splenic or porta nodes.Most GEJ cancers can be safely treated without elective inclusion of splenic/porta nodes.
| S-EPMC4335306 | biostudies-literature