A Phase 2 study of nivolumab in combination with modified FOLFIRINOX for metastatic pancreatic cancer.

Background: Nivolumab with modified FOLFIRINOX (mFOLFIRINOX) may have additive antitumour effects while minimising chemotherapy cytotoxicity. We assessed the efficacy and safety of nivolumab+mFOLFIRINOX in metastatic pancreatic cancer.

Methods: Thirty-one treatment-naïve patients aged ≥20 years with metastatic unresectable/recurrent pancreatic cancer (≥1 measurable lesion per Response Evaluation Criteria in Solid Tumours version 1.

A Phase 2 Study of Encorafenib in Combination with Binimetinib in Patients with Metastatic -Mutated Thyroid Cancer in Japan.

Driver mutations at V600 are frequently identified in papillary thyroid cancer and anaplastic thyroid cancer (ATC), in which BRAF inhibitors have shown clinical effectiveness. This Japanese phase 2 study evaluated the efficacy and safety of a BRAF inhibitor, encorafenib, combined with an MEK inhibitor, binimetinib, in patients with V600-mutated thyroid cancer. This phase 2, open-label, uncontrolled study was conducted at 10 institutions targeted patients with V600-mutated locally advanced or distant metastatic thyroid cancer not amenable to curative treatment who became refractory/intolerant to ≥1 previous vascular endothelial growth factor receptor-targeted regimen(s) or were considered ineligible for those.

Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial.

Background: The additive or synergistic sustained antitumour effect of immune checkpoint inhibitors in combination with oxaliplatin-based chemotherapy has previously been reported. We investigated the efficacy of nivolumab plus oxaliplatin-based chemotherapy versus placebo plus oxaliplatin-based chemotherapy as first-line therapy for patients with HER2-negative, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer.

Methods: We did a randomised, multicentre, double-blind, placebo-controlled, phase 2-3 trial (ATTRACTION-4) at 130 centres (hospitals, cancer centres, and medical centres) across Japan, South Korea, and Taiwan.

A phase II trial of capecitabine plus cisplatin (XP) for patients with advanced gastric cancer with early relapse after S-1 adjuvant therapy: XParTS-I trial.

Backgrounds: In Japan, standard regimens for advanced gastric cancer (AGC) include S-1 chemotherapy. The standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine alone is platinum-based chemotherapy, while the standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine plus platinum is second-line chemotherapy. To evaluate the efficacy and safety of capecitabine plus cisplatin (XP) treatment for AGC patients who relapse within 6 months after S-1-based therapy, we conducted a multicenter phase II trial (NCT01412294).

A phase II study of 5-fluorouracil/L-leucovorin/oxaliplatin (mFOLFOX6) in Japanese patients with metastatic or unresectable small bowel adenocarcinoma.

Background: Several studies have suggested that chemotherapy prolonged survival in patients with metastatic or recurrent small bowel adenocarcinoma (SBA); however, there is still no standard chemotherapy regimen. Here, we evaluated the efficacy and safety of a 5-fluorouracil (5-FU)/L-leucovorin (l-LV)/oxaliplatin (mFOLFOX6) protocol as a first-line therapy for patients with SBA.

Patients And Methods: This was a multicenter, single-arm, open-label phase II study.

Neurological Toxicity in Metastatic Colorectal Cancer Patients Treated with Modified FOLFOX6 Plus Bevacizumab.

This study was conducted to investigate the toxicity and efficacy of modified FOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer with particular regard to oxaliplatin-induced neuropathy. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (version 3.0).

Biomarkers of reactive resistance and early disease progression during chemotherapy plus bevacizumab treatment for colorectal carcinoma.

Molecular markers for predicting or monitoring the efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC) remain to be identified. We have now measured the serum concentrations of 25 angiogenesis-related molecules with antibody suspension bead array systems for 25 mCRC patients both before and during treatment in a previously reported phase II trial of FOLFIRI chemotherapy plus bevacizumab. The serum concentration of vascular endothelial growth factor-A (VEGF-A) decreased after the onset of treatment (P < 0.

[Predicting drug efficacy-fluorinated pyrimidines (fluorouracil, S-1 and capecitabine)].

The elucidation in recent years of intracellular signaling mechanisms related to cancer cell growth has been accompanied by increases in both drug development and biomarker research. While treatment strategies using biomarkers have been established and put to clinical use for various types of cancers and medications, most are limited to drugs targeting specific molecules, and none have been established for traditional cytotoxic drugs. For fluoropyrimidines, the standard drugs used in chemotherapy for gastrointestinal cancer, biomarker research has been conducted on targets such as thymidylate synthase(TS), dihydropyrimidine dehydrogenase(DPD), and thymidine phosphorylase(TP).

Phase II clinical trial of second-line FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer: AVASIRI trial.

Objective: FOLFIRI is a standard chemotherapy regimen for the treatment of metastatic colorectal cancer. Although some studies have shown its efficacy in combination with bevacizumab as first-line chemotherapy, there are no data to support FOLFIRI plus bevacizumab as second-line chemotherapy in patients with this form of cancer. The aim of this study was to evaluate the efficacy and safety of FOLFIRI and bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer.

Pharmacokinetic parameters from 3-Tesla DCE-MRI as surrogate biomarkers of antitumor effects of bevacizumab plus FOLFIRI in colorectal cancer with liver metastasis.

Bevacizumab (BV) is an antivascular endothelial growth factor antibody. When administered with other chemotherapeutic drugs, BV-combined regimens prolong survival of colorectal cancer patients. We conducted a phase II trial to confirm the pharmacokinetic parameters from 3-Tesla dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as surrogate biomarkers of BV + FOLFIRI regimen efficacy in colorectal cancer with liver metastases.

Neuroendocrine tumors of the stomach: chemotherapy with cisplatin plus irinotecan is effective for gastric poorly-differentiated neuroendocrine carcinoma.

Background: Neuroendocrine tumors (NETs) occur in various primary sites, but rarely in the stomach. NETs are classified into three types, carcinoids, malignant carcinoids and poorly differentiated neuroendocrine carcinomas (PNECs), whose clinical behavior is different. Currently, clinical outcomes and standard chemotherapy for NETs of the stomach remain unclear.

Vesicocutaneous fistula formation during treatment with sunitinib malate: Case report.

Background: The oral multi-kinase inhibitor sunitinib malate improves the survival of patients with gastrointestinal stromal tumors (GIST) after the disease progresses or intolerance to imatinib mesylate develops. Urinary fistulae arising during treatment with sunitinib for GIST have not been described.

Case Presentation: We describe a 62-year-old female patient diagnosed with unresectable GIST that involved the abdominal wall, urinary bladder wall, bowel, mesentery and peritoneum in the pelvic cavity.

Second-line chemotherapy with irinotecan plus cisplatin after the failure of S-1 monotherapy for advanced gastric cancer.

Background: For advanced gastric cancer (AGC), second-line chemotherapy after the failure of S-1 has not yet been established. The present study aimed to retrospectively evaluate the efficacy and safety of irinotecan plus cisplatin (IP) therapy after the failure of S-1 in patients with AGC.

Methods: The subjects included 87 patients with AGC who received IP therapy as second-line chemotherapy.

[Impact of HER2, EGFR, IGF-1R, and VEGFR expressions on the outcome of chemotherapy for advanced gastric cancer].

We aimed to elucidate the clinical significance of the expressions of HER2, epidermal growth factor receptor (EGFR), insulin-like growth factor receptor (IGF-1R), and vascular endothelial growth factor receptor 1, 2, 3 (VEGF-R1, VEGF-R2, and VEGF-R3) in gastric cancer. The study group comprised 57 patients who had undergone gastrectomy at the National Cancer Center Hospital and subsequently received first-line chemotherapy (S-1 monotherapy [n=29] or irinotecan+cisplatin [n=28]) for recurrent or residual tumors. We performed immunohistochemical analysis of formalin-fixed paraffinembedded specimens of surgically removed primary tumors to determine the expressions of HER2, EGFR, IGF-1R, and VEGFR1 in tumor cells and the expressions of VEGF-R1, VEGF-R2, and VEGF-R3 in tumor stromal vessels.

Sequential chemotherapy with methotrexate and 5-fluorouracil for chemotherapy-naive advanced gastric cancer with disseminated intravascular coagulation at initial diagnosis.

Purpose: Advanced gastric cancer (AGC) rarely presents with disseminated intravascular coagulation (DIC) at the time of diagnosis before treatment with no current standard chemotherapy (CTx) regimen. However the prognosis is extremely poor without CTx. We investigated the effectiveness of sequential CTx with methotrexate and 5-fluorouracil (MF) in chemotherapy-naive AGC patients with DIC.

Combination chemotherapy with cisplatin and irinotecan in patients with adenocarcinoma of the small intestine.

Background: Small-bowel adenocarcinoma (SBA) is a rare tumor that has a poor response to chemotherapy and a poor prognosis. Treatment strategies for SBA have not been clearly established.

Methods: All patients with SBA treated using a combination of cisplatin and irinotecan (IP) as first-line chemotherapy at the National Cancer Center Hospital in Japan between January 1999 and February 2007 were studied retrospectively.

Impact of vascular endothelial growth factor receptor 1, 2, and 3 expression on the outcome of patients with gastric cancer.

Tumor angiogenesis is a multistep interactive process in which vascular endothelial growth factor (VEGF) and its receptors have a major role. However, the clinical significance of these molecules in gastric cancer (GC) remains unclear. Our study group comprised 86 patients who underwent gastrectomy and subsequently received chemotherapy for recurrent or residual tumor.

Relationships of insulin-like growth factor-1 receptor and epidermal growth factor receptor expression to clinical outcomes in patients with colorectal cancer.

Objectives: The present study evaluated the prognostic implications of insulin-like growth factor-1 receptor (IGF-1R), epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER)-2 in patients with colorectal cancer (CRC).

Methods: Our subjects were 91 patients who underwent surgery and subsequently received fluoropyrimidines. Expressions of IGF-1R, EGFR and HER-2 in primary lesions were analyzed immunohistochemically to determine the prognostic significance of these biomarkers.

A phase i study of bolus 5-fluorouracil and leucovorin combined with weekly paclitaxel (FLTAX) as first-line therapy for advanced gastric cancer.

Objective: To determine the dose-limiting toxicity (DLT) and the maximum-tolerated dose (MTD) of combination chemotherapy with leucovorin-modulated weekly bolus 5-fluorouracil (5-FU) and weekly paclitaxel in patients with advanced gastric cancer (GC).

Methods: Chemotherapy-naive patients with histologically proven metastatic or recurrent GC were enrolled. Paclitaxel was administered as a 1-h intravenous (i.

Impact of insulin-like growth factor type 1 receptor, epidermal growth factor receptor, and HER2 expressions on outcomes of patients with gastric cancer.

Purpose: Expression levels of insulin-like growth factor type 1 receptor (IGF-IR), epidermal growth factor receptor (EGFR), and HER2 expressions have been linked to clinical outcomes in several solid tumors. However, the clinical significance of these biomarkers in gastric cancer (GC) remains unclear. This study was designed to delineate the clinical implications of these three biomarkers in GC.

[Eosinophilic gastroenteritis in the esophagus, stomach, and small intestine in a patient with a choking feeling in the esophagus].

A 75-year-old man was admitted to our hospital with the chief complaint of a choking feeling around the esophagus. Laboratory examinations revealed eosinophilia, and high levels of serum immunoglobulin (Ig) E. A computed tomography scan (CT) showed wall thickening of the esophagus and terminal ileum, and ascites around the liver.

[Successful CPT-11 treatment in a patient with pancreatic cancer associated with multiple liver metastases and chronic renal failure].

A 56-year-old woman, who had been receiving treatment for chronic renal failure, was admitted to our Department because of a tumor of the pancreas head and multiple liver masses diagnosed by abdominal CT scans. Gastroduodenoscopy revealed a tumor which had invaded the Vater's papilla; the lesion was histopathologically pancreatic adenocarcinoma. Due to the presence of multiple metastases to the liver, we therefore performed general chemotherapy after obtaining the patient's informed consent (IC).

Alternative splicing in human transcriptome: functional and structural influence on proteins.

Alternative splicing is a molecular mechanism that produces multiple proteins from a single gene, and is thought to produce variety in proteins translated from a limited number of genes. Here we analyzed how alternative splicing produced variety in protein structure and function, by using human full-length cDNAs on the assumption that all of the alternatively spliced mRNAs were translated to proteins. We found that the length of alternatively spliced amino acid sequences, in most cases, fell into a size shorter than that of average protein domain.

[Successful bi-weekly paclitaxel treatment of an AFP-producing gastric cancer patient with peritoneal dissemination and multiple liver metastasis].

The patient was a 71-year-old man. Chemotherapy was conducted in two courses combining TS-1 (120 mg) and CDDP (80 mg) under the diagnosis of AFP-producing gastric cancer with multiple liver metastasis and peritoneal dissemination. Peritoneal dissemination disappeared, liver metastasis almost disappeared after completion of two courses, and the therapeutic efficacy was rated as PR.