Effect of biliary drainage on chemotherapy in patients with biliary tract cancer: an exploratory analysis of the BT22 study.

Background/purpose: Complications from biliary drainage in biliary tract cancer (BTC) may influence the relative dose intensity of chemotherapy or increase adverse events during chemotherapy. BT22 was a randomized phase II trial, the results of which were consistent with those of a phase III trial in non-Japanese that demonstrated the effectiveness of gemcitabine plus cisplatin combination therapy (GC) in BTC. The purpose of this exploratory analysis of the BT22 study was to identify the possible effects of biliary drainage on the efficacy and safety of GC or gemcitabine monotherapy (G).

Phase I/II study of gemcitabine as a fixed dose rate infusion and S-1 combination therapy (FGS) in gemcitabine-refractory pancreatic cancer patients.

Purpose: There is no standard regimen for gemcitabine (Gem)-refractory pancreatic cancer (PC) patients. In a previous phase II trial, S-1 was found to exhibit marginal efficacy. Gem administration by fixed dose rate infusion of 10 mg/m(2)/min (FDR-Gem) should maximize the rate of intracellular accumulation of gemcitabine triphosphate and might improve clinical efficacy.

Radiofrequency ablation for hepatocellular carcinoma induces glypican-3 peptide-specific cytotoxic T lymphocytes.

Glypican-3 (GPC3), a carcinoembryonic antigen, is an ideal target for anticancer immunotherapy against hepatocellular carcinoma (HCC). In this study, we attempted to compare the induction of the GPC3-specific T-cell-mediated immune response after locoregional therapies in HCC patients and tumor-bearing mice. Twenty-seven HCC patients treated with locoregional therapies, including radiofrequency ablation (RFA), surgical resection and transcatheter arterial chemo-embolization (TACE), were prospectively enrolled in this study.

Inhibitor of MEK1/2, selumetinib, for biliary tract cancer.

It is necessary to establish effective chemotherapy to improve the survival of patients with biliary tract cancer. Although the useful of some molecular-targeted agents as first-line therapies has been investigated, none have been found to exert satisfactory efficacy. In this article, we report the results of a Phase II study of selumetinib in patients with metastatic biliary cancer.

Multicenter phase II study of gemcitabine and S-1 combination therapy (GS Therapy) in patients with metastatic pancreatic cancer.

Objective: The aim of this multicenter Phase II study was to assess the efficacy and toxicity of gemcitabine and S-1 combination therapy for metastatic pancreatic cancer.

Methods: Chemotherapy-naïve patients with histologically or cytologically proven metastatic pancreatic adenocarcinoma were eligible for this study. Gemcitabine was administered at a dose of 1000 mg/m(2) over 30 min on days 1 and 8, and oral S-1 at a dose of 40 mg/m(2) twice daily from days 1 to 14, repeated every 3 weeks.

Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma.

Background: In Japan and South Korea, transarterial chemoembolisation (TACE) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown effective and safe in patients with advanced HCC. This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE.

[Two cases of advanced colorectal cancer which demonstrated the reversibility of oxaliplatin-mediated increase in splenic volume].

Hepatic sinusoidal injury arises occasionally after oxaliplatin-based chemotherapy. As a result, portal hypertension associated with splenomegaly occurs in some cases. We report two cases of advanced colorectal cancer which showed splenomegaly after administration of oxaliplatin-based chemotherapy.

[Managements for jaundice].

Jaundice is a yellowish pigmentation of skin and mucous membranes caused by hyperbilirubinemia, which itself has various causes. Jaundice related to malignant tumors is classified as obstructive jaundice. This disease proceeds from biliary tract obstruction and liver failure by progression of intrahepatic tumors, including metastases from other malignancies.

Sorafenib-associated hand-foot syndrome in Japanese patients.

Sorafenib (Nexavar) is an oral multi-kinase inhibitor that targets tumor growth and angiogenesis, having encouraging efficacy and tolerability in patients with metastatic renal cell carcinoma (RCC) and other tumors. However, hand-foot syndrome (HFS), a frequently reported adverse event under sorafenib treatment, sometimes causes interruption of the treatment or dose reduction. This study was conducted to review sorafenib-associated HSF in Japanese patients, to facilitate improvement of the management of HFS in clinical practice.

Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study.

Background: Axitinib is a potent, selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. A randomised phase 2 trial of gemcitabine with or without axitinib in advanced pancreatic cancer suggested increased overall survival in axitinib-treated patients. On the basis of these results, we aimed to assess the effect of treatment with gemcitabine plus axitinib on overall survival in a phase 3 trial.

Targeted therapy for biliary tract cancer.

It is necessary to establish effective chemotherapy to improve the survival of patients with biliary tract cancer, because most of these patients are unsuitable candidates for surgery, and even patients undergoing curative surgery often have recurrence. Recently, the combination of cisplatin plus gemcitabine was reported to show survival benefits over gemcitabine alone in randomized clinical trials conducted in the United Kingdom and Japan. Thus, the combination of cisplatin plus gemcitabine is now recognized as the standard therapy for unresectable biliary tract cancer.

Phase II study of erlotinib plus gemcitabine in Japanese patients with unresectable pancreatic cancer.

Erlotinib combined with gemcitabine has not been evaluated in Japanese patients with unresectable pancreatic cancer. This two-step phase II study assessed the safety and pharmacokinetics of erlotinib 100 mg/day (oral) plus gemcitabine 1000 mg/m(2) (i.v.

The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and the burden of this devastating cancer is expected to increase further in coming years. The collection and analysis of epidemiologic HCC data will play a critical role in guiding future disease prevention strategies and optimizing patient management. Previous epidemiologic studies have highlighted striking global variations in the incidence of HCC, which is particularly high in much of east Asia and sub-Saharan Africa, and lower, but on the increase, in North America and most of Europe.

A phase I/II study of combined chemotherapy with mitoxantrone and uracil/tegafur for advanced hepatocellular carcinoma.

Objective: The aim was to determine the recommended dose of combined chemotherapy with mitoxantrone and uracil/tegafur (Phase I part) and to clarify its efficacy and safety in patients with advanced hepatocellular carcinoma at the recommended dose (Phase II part).

Methods: Patients eligible had histologically confirmed, chemo-naive advanced hepatocellular carcinoma and were amenable to established forms of treatment. The therapy consisted of mitoxantrone administered intravenously at one of three dosages (6, 8 and 10 mg/m(2)/day) on day 1 and uracil/tegafur administered orally at 300 mg/m(2) from day 1 through day 21.

Lessons from the comparison of two randomized clinical trials using gemcitabine and cisplatin for advanced biliary tract cancer.

There had been no standard chemotherapy established for advanced biliary tract cancer (BTC) until 2009, when the combination of cisplatin and gemcitabine (GC) was adopted as a first line standard chemotherapy option based on the results from two randomized studies: ABC-02, a UK investigator-initiated trial and the largest randomized phase III study in this tumor type with 410 patients; and BT22, a Japanese, industry-sponsored, randomized phase II study with 83 patients. In this review, investigators from both studies collaborated to compare protocols, patient characteristics, and outcomes of both studies including sub-analyses of study results. Although both studies showed GC combination therapy to be more effective than monotherapy, a detailed comparison revealed disparities between efficacy and safety end-points between the studies, which did not necessarily arise from different populations but from differences in protocol design.

[Two cases of colorectal cancer presenting with periodic, transient elevation of serum iron after chemotherapy including irinotecan].

It is known that the serum iron level shows a transient elevation after chemotherapy in some cases; however, the cause of this phenomenon has not been clearly described. We report two cases of colorectal cancer whose serum iron level demonstrated recurrent elevation after administration of irinotecan as a second-line chemotherapy. The transferrin saturation rate showed marked elevation together with serum iron.

Treatment efficacy/safety and prognostic factors in patients with advanced biliary tract cancer receiving gemcitabine monotherapy: an analysis of 100 cases.

Aim: The purpose of this study was to elucidate the treatment efficacy and safety of gemcitabine monotherapy, and to identify prognostic factors in patients with advanced biliary tract cancer receiving this therapy.

Method: The data of 100 patients with advanced biliary tract cancer who were treated with gemcitabine as first-line chemotherapy were reviewed retrospectively.

Results: One patient showed complete response (1.

Eastern Asian expert panel opinion: designing clinical trials of molecular targeted therapy for hepatocellular carcinoma.

The largest burden of hepatocellular carcinoma (HCC) lies in Asia, secondary to hepatitis B virus (HBV) infection. Improved survival with sorafenib has fostered new research but many challenges remain in designing clinical trials. The disease, its management, and populations affected by it are heterogeneous worldwide and within Asia.

[A case of mucosa-associated lymphoid tissue lymphoma with penicillin allergy successfully treated with levofloxacin, minomycin and rabeprazole].

A 52-year-old Japanese woman was referred to our Institute because of Helicobacter pylori(H. pylori)-positive gastric mucosa-associated lymphoid tissue(MALT)lymphoma. Since she had a penicillin allergy, we could not eradicate H.

Phase I/II study of the pharmacokinetics, safety and efficacy of S-1 in patients with advanced hepatocellular carcinoma.

S-1, an oral fluoropyrimidine derivative, has been shown to be clinically effective against various solid tumors, and preclinical studies have demonstrated activity against hepatocellular carcinoma. We conducted a phase I/II study in patients with advanced hepatocellular carcinoma to examine the pharmacokinetics, recommended dose, safety and efficacy of S-1. In phase I, the administered dose of S-1 was approximately 64 mg/m(2) per day in three patients (level 1) and approximately 80 mg/m(2) per day in six patients (level 2).

Liver Cancer Working Group report.

Hepatocellular carcinoma is a highly prevalent disease in many Asian countries, accounting for 75-80% of victims worldwide. The incidence of hepatocellular carcinoma varies enormously across Asia, but tends to follow the incidences of hepatitis B infection and liver cirrhosis. The incidence and etiology of hepatocellular carcinoma in Japan are different from the rest of Asia, but similar to that in Western countries because hepatitis C infection is the main etiological factor in Japan.

[Two cases of colorectal cancer presenting with periodic, transient elevation of serum iron due to hemolysis after chemotherapy including 5-FU].

The serum iron level reportedly shows transient elevation after chemotherapy in some cases. However, the cause of this phenomenon has not been clearly described. We report two cases of colorectal cancer whose serum iron level demonstrated recurrent elevation after chemotherapy.

Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan (2009 Revised Version).

The World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST) are inappropriate to assess the direct effects of treatment on the hepatocellular carcinoma (HCC) by locoreginal therapies such as radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE). Therefore, establishment of response evaluation criteria solely devoted for HCC is needed urgently in the clinical practice as well as in the clinical trials of HCC treatment, such as molecular targeted therapies, which cause necrosis of the tumor. Response Evaluation Criteria in Cancer of the Liver (RECICL) was revised in 2009 by Liver Cancer Study Group of Japan based on the 2004 version of RECICL, which was commonly used in Japan.

Randomized phase II study of gemcitabine plus S-1 combination therapy vs. S-1 in advanced biliary tract cancer: Japan Clinical Oncology Group Study (JCOG0805).

A randomized Phase II selection design trial comparing gemcitabine plus S-1 combination therapy with S-1 monotherapy for chemo-naïve unresectable or recurrent biliary tract cancer patients was started in Japan. The aim of this trial is to evaluate the efficacy and safety of the two regimens and to determine which is more promising as a test arm regimen to be compared with the current standard regimen, gemcitabine plus cisplatin, in a subsequent Phase III trial. Patients with unresectable or recurrent biliary tract cancer are randomized to either gemcitabine plus S-1 combination therapy arm or S-1 monotherapy arm.

Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan.

Background: A British randomised study of gemcitabine plus cisplatin (GC) combination showed promising results in biliary tract cancer (BTC) patients. In our study, we evaluated the efficacy and safety of this combination compared with gemcitabine alone (G) in Japanese BTC patients.

Methods: Overall, 84 advanced BTC patients were randomised to either cisplatin 25 mg m(-2) plus gemcitabine 1000 mg m(-2) on days 1, 8 of a 21-day cycle (GC-arm), or single-agent gemcitabine 1000 mg m(-2) on days 1, 8 and 15 of a 28-day cycle (G-arm).