A Different Kind of Relapse: Ethanol as an Additive in Chemotherapy Formulations

Some chemotherapy formulations contain ethanol as a solvent which can become relevant for medical and nonmedical reasons. Only a few studies have tried to quantify the effects of ethanol in chemotherapy preparations. Furthermore, the alcohol amount highly depends on the specific formulation, with some variation among different manufacturers. Although the actual increase in blood alcohol levels after ethanol-based chemotherapies seems to be limited, the FDA recently released a warning that docetaxel may cause symptoms of alcohol intoxication. Here, we report on a patient with breast cancer who experienced a relapse of alcohol abuse after a single docetaxel infusion. We hypothesize a causal relationship with the ethanol-containing docetaxel infusion. Today, no guidelines exist for the use of ethanol-based chemotherapy, and patient consent forms do not address this matter. We conclude that physicians prescribing chemotherapy and patients should be aware of the potential risks of ethanol-containing infusions and nonethanol- based alternatives should be discussed when needed or desired by the patient. This could be facilitated by revised patient consent forms

Molecular Targets for Gastric Cancer Treatment and Future Perspectives from a Clinical and Translational Point of View

Gastric cancer is a leading cause of cancer death worldwide. Systemic treatment comprising chemotherapy and targeted therapy is the standard of care in advanced/metastatic gastric cancer. Comprehensive molecular characterization of gastric adenocarcinomas by the TCGA Consortium and ACRG has resulted in the definition of distinct molecular subtypes. These efforts have in parallel built a basis for the development of novel molecularly stratified treatment approaches. Based on this molecular characterization, an increasing number of specific genomic alterations can potentially serve as treatment targets. Consequently, the development of promising compounds is ongoing. In this review, key molecular alterations in gastric and gastroesophageal junction cancers will be addressed. Finally, the current status of the translation of targeted therapy towards clinical applications will be reviewed

Randomized controlled trial of S-1 maintenance therapy in metastatic esophagogastric cancer – the multinational MATEO study

Background: The optimal duration of firstline chemotherapy in metastatic esophagogastric cancer is unknown. In most clinical trials therapy was given until tumour progression or limiting toxicity. Maintenance concepts aiming to prolong the duration of response and maintain quality of life have been established in other tumour types but not in esophagogastric cancer. S-1 is an oral fluoropyrimidine with proven efficacy in metastatic esophagogastric cancer. Methods: The Maintenance Teysuno® (S-1) in esophagogastric cancer (MATEO) trial is a multinational, randomized phase II study that explores the role of S-1 maintenance therapy in Her-2 negative, advanced esophagogastric adenocarcinoma. After a 12-week firstline platinum-fluoropyrimidine-based chemotherapy patients without tumour progression are randomized in a 2:1 allocation to receive S-1 alone or continue with the same regimen as during the primary period. The primary endpoint is overall survival. Secondary endpoints include safety and toxicity, progression-free survival and quality of life. Correlative biomarker analyses focus on the identification of a subgroup of patients with a prolonged benefit from S-1 based maintenance therapy. Discussion: MATEO will be the first trial to define the role of a S-1 based maintenance therapy in patients having received a platinum-based firstline chemotherapy. Trial registration: NCT02128243 (date of registration: 29–04-2014)

Influence of Taxanes on Treatment Sequence in Gastric Cancer

Background: Adenocarcinoma of the stomach and esophagogastric junction (EGJ) remains a tumor entity with a poor prognosis. While meaningful advances have been made in the treatment of other solid tumors in the past years, numerous phase III studies in gastric cancer have had negative outcomes. Successes of targeted therapies so far include the introduction of trastuzumab in the first-line treatment of HER2-positive gastric cancer, and second-line anti-angiogenic treatment with the anti-VEGF-2 receptor antibody ramucirumab. Taxanes have become established in the perioperative setting and in second-line treatment and have set new standards. However, evidence for improved overall survival in the first-line treatment of advanced gastric cancer with taxanes is not convincing. Methodology: Expert consensus discussion on the scientific and clinical evidence for sequential systemic treatment for advanced gastric and EGJ cancer, taking into account data clinical outcomes from randomized controlled phase II and phase III trials. Summary: In first-line treatment of advanced gastric cancer, taxanes in combination with a platinum- and 5-fluorouracil-based regimen are generally not recommended because they lack a survival benefit and confer high toxicity. However, taxanes in first-line can be a treatment option for patients presenting with high tumor burden and strong pressure to achieve remission. Since the publication of several positive studies in second- and third-line therapy, sequential therapy is playing an increasingly important role in metastatic gastric and EGJ cancer. Key Message: Standard of care for the first-line treatment of gastric cancer is a platinum-fluoropyrimidine chemotherapy doublet combination. The standard of care after failure of platinum-based first-line therapy is ramucirumab in combination with paclitaxel. Data supporting this combination after previous taxane therapy are not yet available

Young patients with cancer and a digital social network: the voice beyond the clinic.

INTRODUCTION: Digital social networks have become a key player in the ecosystem of young patients with cancer, with regard to their unique perspectives and unmet needs. This study aims to investigate the web-based social community tools and to characterise the user profile, unmet needs and goals of young patients with cancer. METHODS: A web-based survey was distributed via large-scale social network designated for young patients with cancer (age 18-45 years) Stop Cancer. The survey collected demographic data and oncological status. Primary outcome was potential goals of accessing the network; secondary outcomes were emotional impact, effect of disease status, education, marital status and employment, on user satisfaction rate. RESULTS: The survey was available for 5 days (10/2018) and was filled by 523 participants. Breast cancer, haematological malignancies and colorectal cancer were the most common diagnoses. The majority had non-metastatic disease at diagnosis, 79% had no evidence of disease at time of the survey. Forty-five per cent considered the network as a reliable source for medical information. Academic education was associated with higher satisfaction from the platform. There were no differences between cancer survivors and patients with active disease in patterns of platform usage. The social network had an allocated section for 'patient mentoring' of newly diagnosed members by survivors. DISCUSSION: Our study portrayed the user prototype of a social digital network among young adult patients with cancer, indicating challenging trends. Whereas social media may prove a powerful tool for patients and physicians alike, it may also serve as a research tool to appraise wide practices within a heterogeneous population. Nevertheless, it acts as a double-edged sword in the setting of uncontrolled medical information. It is our role as healthcare providers to join this race and play an active role in shaping its medical perspectives

Immunotherapy of Peritoneal Carcinomatosis with the Antibody Catumaxomab in Colon, Gastric, or Pancreatic Cancer: An Open-Label, Multicenter, Phase I/II Trial

Background: Peritoneal carcinomatosis (PC) is common in gastrointestinal (GI) cancer and there is no effective standard treatment. We investigated the tolerability and maximum tolerated dose (MTD) of the trifunctional antibody catumaxomab in patients with PC. Methods: In this open-label, phase I/II clinical trial, patients with epithelial cell adhesion molecule (EpCAM)-positive PC from GI cancer received 4 sequential intraperitoneal catumaxomab infusions: day 0: 10 mu g; day 3: 10 or 20 mu g; day 7: 30, 50, or 100 mu g; and day 10: 50, 100, or 200 mu g. Dose escalation was guided by dose-limiting toxicities. Results: The MTD was 10, 20, 50, and 200 mu g on days 0, 3, 7, and 10, respectively. Catumaxomab had an acceptable safety profile: Most common treatment-related adverse events (at the MTD) were fever, vomiting, and abdominal pain. At final examination, 11/17 evaluable patients (65%) were progression free: 1 patient had a complete and 3 a partial response. Median overall survival from the time of diagnosis of PC was 502 days. Conclusions: Intraperitoneal catumaxomab is a promising option for the treatment of PC from GI cancer

Definition of oligometastatic esophagogastric cancer and impact of local oligometastasis-directed treatment: A systematic review and meta-analysis

BACKGROUND Local treatment (metastasectomy or stereotactic radiotherapy) for oligometastatic disease (OMD) in patients with esophagogastric cancer may improve overall survival (OS). The primary aim was to identify definitions of esophagogastric OMD. A secondary aim was to perform a meta-analysis of OS after local treatment versus systemic therapy alone for OMD. METHODS Studies and study protocols reporting on definitions or OS after local treatment for esophagogastric OMD were included. The primary outcome was the maximum number of organs/lesions considered OMD and the maximum number of lesions per organ (i.e. 'organ-specific' OMD burden). Agreement was considered to be either absent/poor (< 50%), fair (50%-75%), or consensus (≥ 75%). The secondary outcome was the pooled adjusted hazard ratio (aHR) for OS after local treatment versus systemic therapy alone. The ROBINS tool was used for quality assessment. RESULTS A total of 97 studies, including 7 study protocols, and 2 prospective studies, were included. OMD was considered in 1 organ with ≤ 3 metastases (consensus). 'Organ-specific' OMD burden could involve bilobar ≤ 3 liver metastases, unilateral ≤ 2 lung metastases, 1 extra-regional lymph node station, ≤ 2 brain metastases, or bilateral adrenal gland metastases (consensus). Local treatment for OMD was associated with improved OS compared with systemic therapy alone based on 6 non-randomized studies (pooled aHR 0.47, 95% CI: 0.30-0.74) and for liver oligometastases based on 5 non-randomized studies (pooled aHR 0.39, 95% CI: 0.22-0.59). All studies scored serious risk of bias. CONCLUSIONS Current literature considers esophagogastric cancer spread limited to 1 organ with ≤ 3 metastases or 1 extra-regional lymph node station to be OMD. Local treatment for OMD appeared associated with improved OS compared with systemic therapy alone. Prospective randomized trials are warranted

VESTIGE: Adjuvant Immunotherapy in Patients With Resected Esophageal, Gastroesophageal Junction and Gastric Cancer Following Preoperative Chemotherapy With High Risk for Recurrence (N+ and/or R1): An Open Label Randomized Controlled Phase-2-Study

Background: Perioperative chemotherapy plus surgery is one recommended standard treatment for patients with resectable gastric and esophageal cancer. Even with a multimodality treatment more than half of patients will relapse following surgical resection. Patients who have a poor response to neoadjuvant chemotherapy and have an incomplete (R1) resection or have metastatic lymph nodes in the resection specimen (N+) are especially at risk of recurrence. Current clinical practice is to continue with the same chemotherapy in the adjuvant setting as before surgery. In the phase II randomized EORTC VESTIGE trial (NCT03443856), patients with high risk resected gastric or esophageal adenocarcinoma will be randomized to either adjuvant chemotherapy (as before surgery) or to immunotherapy with nivolumab and low dose ipilimumab (nivolumab 3 mg/kg IV Q2W plus Ipilimumab 1 mg/kg IV Q6W for 1 year). The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety and toxicity, and quality of life. This is an open label randomized controlled multi-center phase-2 superiority trial. Patients will be randomized in a 1:1 ratio to study arms. The trial will recruit 240 patients; recruitment commenced July 2019 and is anticipated to take 30 months. Detailed inclusion/exclusion criteria, toxicity management guidelines, and statistical plans for EORTC VESTIGE are described in the manuscript. Clinical Trial Registration: The trial is registered with www.ClinicalTrials.gov, identifier: NCT03443856