Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer.

Background: Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate consisting of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. The drug may have efficacy in patients with HER2-positive advanced gastric cancer.

Methods: In an open-label, randomized, phase 2 trial, we evaluated trastuzumab deruxtecan as compared with chemotherapy in patients with HER2-positive advanced gastric cancer.

Prognostic role of body composition parameters in gastric/gastroesophageal junction cancer patients from the EXPAND trial.

Background: Body fat and/or muscle composition influences prognosis in several cancer types. For advanced gastric and gastroesophageal junction cancer, we investigated which body composition parameters carry prognostic information beyond well-established clinical parameters using robust model selection strategy such that parameters identified can be expected to generalize and to be reproducible beyond our particular data set. Then we modelled how differences in these parameters translate into survival outcomes.

Quality of life on TSU-68: Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline.

Aim: The aim of this study is to investigate whether the addition of TSU-68 would affect on the quality of life (QOL) of Korean metastatic breast cancer patients treated with docetaxel.

Methods: Sixty-three of 78 patients completed the baseline QOL questionnaires and at least one follow-up questionnaire comprising questions from the Korean Functional Assessment of Cancer Therapy-Breast (FACT-B), hospital anxiety and depression scale (HAD), the shortened form of the profile of mood states (BPOMS), and anticipation and anxiety for treatment scale. Changes in QOL scores from baseline were compared by analysis of covariance at each time point (6, 12 weeks, 9, 12 and 18 months) and at the end of treatment (EOT), and the longitudinal changes over time were evaluated by repeated measure analysis.

Circulating Plasma Biomarkers for TSU-68, an Oral Antiangiogenic Agent, in Patients with Metastatic Breast Cancer.

Purpose: This study analyzed the role of plasma biomarkers for TSU-68 in a previous phase II trial comparing TSU-68 plus docetaxel and docetaxel alone in patients with metastatic breast cancer.

Materials And Methods: A total of 77 patients were eligible for this study (38 in the TSU-68 plus docetaxel arm and 39 in the docetaxel alone arm). Blood samples were collected prior to the start of each cycle, and vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-AA, -AB, -BB, fibroblast growth factor, M30, C-reactive protein (CRP), and interleukin 6 (IL-6) levels were measured using enzyme linked immunosorbent assay.

Quality of life in the trastuzumab for gastric cancer trial.

Background: The Trastuzumab for Gastric Cancer phase III trial demonstrated that combining trastuzumab with chemotherapy significantly improved overall survival compared with chemotherapy alone in HER2-positive advanced gastric or gastroesophageal junction cancer. We report health-related quality of life (HRQoL) and quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) results from this trial.

Patients And Methods: Patients were randomized to receive six cycles of chemotherapy given every 3 weeks (capecitabine or fluorouracil, plus cisplatin) either alone or combined with administration of trastuzumab every 3 weeks until disease progression.

Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline: randomized phase II multicenter trial.

The novel oral antiangiogenic agent TSU-68 was investigated in patients with metastatic breast cancer. Patients with anthracycline-pretreated metastatic breast cancer were randomly assigned to receive either TSU-68 400 mg twice daily on days 1-21 plus docetaxel 60 mg/m(2) on day 1 every 3 weeks, or docetaxel 60 mg/m(2) on day 1 every 3 weeks. The primary endpoint was progression-free survival.

Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial.

Purpose: Open-label, phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer.

Patients And Methods: Patients were stratified and randomly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day.

Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study.

Purpose: The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer.

Patients And Methods: Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC.

Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial.

Background: Patients with advanced gastric cancer have a poor prognosis and few efficacious treatment options. We aimed to assess the addition of cetuximab to capecitabine-cisplatin chemotherapy in patients with advanced gastric or gastro-oesophageal junction cancer.

Methods: In our open-label, randomised phase 3 trial (EXPAND), we enrolled adults aged 18 years or older with histologically confirmed locally advanced unresectable (M0) or metastatic (M1) adenocarcinoma of the stomach or gastro-oesophageal junction.

Evaluation of the willingness-to-pay for cancer treatment in Korean metastatic breast cancer patients: a multicenter, cross-sectional study.

Aims: To evaluate the inherent value of breast cancer therapy a willingness-to-pay (WTP) study was conducted in Korean patients with metastatic breast cancer.

Methods: Patients were prospectively enrolled from four study centers and completed quality of life questionnaires to reflect their status pre-cancer and their current health status. Clinical and socioeconomic data were collected to characterize the population and utilize during modeling.

Identification of GABRA1 and LAMA2 as new DNA methylation markers in colorectal cancer.

Aberrant methylation of CpG islands in the promoter region of genes is a common epigenetic phenomenon found in early cancers. Therefore conducting genome-scale methylation studies will enhance our understanding of the epigenetic etiology behind carcinogenesis by providing reliable biomarkers for early detection of cancer. To discover novel hypermethylated genes in colorectal cancer by genome-wide search, we first defined a subset of genes epigenetically reactivated in colon cancer cells after treatment with a demethylating agent.

Genetic analysis of liver metastatic cell lines with different metastatic potential.

Metastasis is the major feature of malignant tumors that causes 90% of cancer deaths. Our laboratory has already established liver metastatic clones with YCC-16, isolated from the blood of a gastric cancer patient and expanded in vitro culture using a repeated orthotopic implantation method, and had reported biologic behaviour of the parental YCC-16, the orthotopic primary S1L0, and S1L1, S2L2 and S3L3 liver metastatic clones. Here, using these cell lines, we screened from chromosomal abnormalities using karyotype analysis and micro-CGH matching.

Identification of novel gastric cancer-associated CNVs by integrated analysis of microarray.

Background: Microarray-CGH facilitates analysis of cancer-associated genomic differences between normal and tumor tissues and provides a genome-wide assessment of copy number variations (CNVs).

Methods: To identify CNVs and their clinical significance in gastric cancer, Microarray-CGH was performed to identify CNVs with genomic DNA (gDNA) from normal placenta tissue, peripheral blood mononuclear cells (PBMCs), and normal gastric tissue.

Results: A total of 20 CNVs, including 8 novel CNVs, were identified by Microarray-CGH.

Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes.

Limited proven treatment options exist for patients with metastatic breast cancer (MBC) resistant to anthracycline and taxane treatment. Ixabepilone, a novel semisynthetic analog of epothilone B, has demonstrated single-agent activity in MBC resistant to anthracyclines and taxanes. In combination with capecitabine in a phase III trial (CA163-046) in this setting, ixabepilone prolonged progression-free survival and increased objective response rate relative to capecitabine (Thomas et al.

Activity of ixabepilone in oestrogen receptor-negative and oestrogen receptor-progesterone receptor-human epidermal growth factor receptor 2-negative metastatic breast cancer.

Oestrogen receptor (ER)-negative breast cancer, including oestrogen receptor-, progesterone receptor- and human epidermal growth factor receptor 2-negative (ER/PR/HER2-negative) breast cancer, is more aggressive than ER-positive disease. A major limitation in the treatment of ER-negative disease subtypes is the inherent insensitivity to hormonal agents (tamoxifen, aromatase inhibitors) that are widely used in the treatment of breast cancer. Thus, therapeutic options for poor prognosis patients with ER-negative breast cancer are limited to a handful of chemotherapeutic agents, and new agents are needed to improve the treatment of this disease.

A multi-center phase II study of S-1 plus paclitaxel as first-line therapy for patients with advanced or recurrent unresectable gastric cancer.

Purpose: This study was conducted to evaluate the safety and efficacy of S-1 and paclitaxel combination therapy for patients with advanced gastric cancer.

Methods: Eligible patients had previously untreated advanced or relapsed gastric cancer with measurable lesion(s) and an ECOG PS of 0-2. Treatment consisted of S-1 35 mg/m(2) p.

Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment.

Purpose: Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed to compare ixabepilone plus capecitabine versus capecitabine alone in anthracycline-pretreated or -resistant and taxane-resistant locally advanced or metastatic breast cancer.

Cellular adjustment of gastric cancer for hepatic metastasis in successive orthotopic implantation model.

In order to examine the mechanisms of hepatic metastasis in gastric cancer, a repeated orthotopic implantation method was used in nude mice with YCC-16, which was isolated from the blood of a gastric cancer patient. This study compared the biological and cytogenetic phenotypes of the five cell lines, the parental YCC-16, the orthotopic primary S1L0 and the 3 subsequent liver metastatic clones of S1L1, S2L2 and S3L3. E-cadherin and DAG1 gene expression levels were measured using real-time PCR.

Synchronous coexpression of epidermal growth factor receptor and cyclooxygenase-2 in carcinomas of the uterine cervix: a potential predictor of poor survival.

Purpose: To evaluate the potential of the new prognostic information gained by analyzing the coexpression of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in cervical cancer patients.

Experimental Design: Sixty-eight patients with International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix, who underwent concurrent chemoradiotherapy between 1993 and 1996, were divided into the following four groups according to their immunoreactivities for EGFR and COX-2 in paraffin-embedded sections: (a). the EGFR-negative/COX-2-negative group (n = 11); (b).