Hiraku Fukushima

Three cases of acute or fulminant hepatitis E caused by ingestion of pork meat and entrails in Hokkaido, Japan: Zoonotic food-borne transmission of hepatitis E virus and public health concerns.

Aim:  In developed countries including Japan, the transmission route of indigenous hepatitis E virus (HEV) infection is obscure. Accordingly, public health implications of indigenous HEV infection have not been well addressed. The aim of this study was to clarify the route of transmission of a small outbreak of acute hepatitis E and assess the public health implications of indigenous zoonotic HEV transmission.

Phase II Study of Combined Treatment with Irinotecan and S-1 (IRIS) in Patients with Inoperable or Recurrent Advanced Colorectal Cancer (HGCSG0302)

Objectives: This phase II study was designed to evaluate the efficacy and safety of oral fluoropyrimidine S-1 plus irinotecan (IRIS regimen) in patients with previously untreated metastatic colorectal cancer. Methods: The response rate was the primary endpoint. Safety, progression-free survival time, and median survival time were secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer. Irinotecan was administered at a dose of 100 mg/m2 (on days 1 and 15). S-1 (40 mg/m2) was administered for 2 weeks (on days 1 to 14) and followed by a 2-week rest. Results: Forty patients were enrolled. Four patients had grade 4 neutropenia, and six patients had grade 3 diarrhea. No other serious hematologic or nonhematologic adverse reactions occurred, and all patients received IRIS safely on an outpatient basis. The response rate was 52.5% (95% confidence interval [CI], 36.1–68.5%). Median progression-free survival was 8.6 months (95% CI, 5.3–11.9), and median survival time was 23.4 months (95% CI, 15.9–30.8). Conclusions: IRIS produced a high response rate and could be given safely. IRIS may become a first-line treatment for inoperable or recurrent advanced colorectal cancer.

Randomized controlled trial on the skin toxicity of panitumumab in Japanese patients with metastatic colorectal cancer: HGCSG1001 study; J-STEPP

AIM We planned a randomized, open-label trial to evaluate differences between pre-emptive and reactive skin treatment for panitumumab (Pmab)-associated skin toxicities in Japanese patients with metastatic colorectal cancer. PATIENTS & METHODS Patients receiving third-line Pmab-containing regimens were randomized to pre-emptive or reactive treatment. The primary end point was the cumulative incidence of ≥grade 2 skin toxicities during 6 weeks. Retrospectively, a dermatologist reviewed skin toxicities, in a blinded manner. RESULTS A total of 95 patients were enrolled (pre-emptive: 47, reactive: 48). The primary end point was achieved (21.3 and 62.5% [risk ratio: 0.34; p < 0.001], for pre-emptive and reactive treatment, respectively). A similar trend was observed in central review. CONCLUSION Pre-emptive skin treatment could reduce the severity of Pmab-associated skin toxicities in Japanese metastatic colorectal cancer patients.

Phase II study of combined chemotherapy with irinotecan and S-1 (IRIS) plus bevacizumab in patients with inoperable recurrent or advanced colorectal cancer

Abstract Background. In Japan, a study comparing the effectiveness and safety of irinotecan plus S-1 (IRIS) with those of a combination of 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as second-line treatment in patients with advanced or recurrent colorectal cancer demonstrated that IRIS was non-inferior to FOLFIRI. We previously reported that IRIS is also effective as first-line treatment. Patients and methods. Eligibility criteria included inoperable recurrent colorectal cancer with a confirmed diagnosis of adenocarcinoma, age ≥20 years, and no history of prior chemotherapy. S-1 (40–60 mg twice daily) was given orally on Days 1 to 14, and irinotecan (100 mg/m2) and bevacizumab (5 mg/kg) were given intravenously on Days 1 and 15 of a 28-day cycle. The primary endpoint was safety. The secondary endpoints included overall response (OR), progression-free survival (PFS), and overall survival (OS). Results. A total of 52 eligible patients were enrolled from October 2007 through March 2009. In safety analysis, the incidences of grade 3 or 4 adverse reactions were as follows: neutropenia, 27%; hypertension, 21%; and diarrhea, 17%. The overall response rate was 57.7%. Median progression-free survival was 16.7 months. Conclusion. IRIS plus bevacizumab is a well-tolerated, highly effective chemotherapeutic regimen that is easy to administer.

Open‐label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron

The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1–3 in combination with palonosetron (PALO), a second‐generation 5‐HT3 receptor antagonist, for chemotherapy‐induced nausea and vomiting (CINV) in non‐anthracycline and cyclophosphamide (AC) moderately‐emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi‐center, randomized, open‐label, non‐inferiority design. Patients who received non‐AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2–3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non‐inferiority margin was set at −15% (study treatment group − control group). From April 2011 to March 2013, 305 patients who received non‐AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non‐inferior to PALO plus DEX days 1–3 (difference, 2.5%; 95% confidence interval [CI]: −7.8%–12.8%; P‐value for non‐inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti‐emetic DEX administration on days 2–3 may be eliminated when used in combination with PALO in patients receiving non‐AC MEC.

A Prospective Observational Study on Effect of Short‐Term Periodic Steroid Premedication on Bone Metabolism in Gastrointestinal Cancer (ESPRESSO‐01)

This study is an evaluation of the effect of gastrointestinal cancer chemotherapy with short‐term periodic steroid premedication on bone metabolism. Primary endpoints were changes in bone mineral densities and metabolic bone turnover 16 weeks after initiation of chemotherapy.

Observational cohort study of first-line bevacizumab combined with chemotherapy in metastatic colorectal cancer (HGCSG0802): Sub-group analysis by KRAS Exon2 status.

782 Background: A few reports have shown the efficacy of bevacizumab (BV) independent of the KRAS Exon2 mutational status (KRAS). We performed a sub-group analysis by KRAS from the HGCSG0802 observ...

The efficacy of first-line IRIS with or without bevacizumab in patients with metastatic colorectal cancer: Including multivariate analysis of two phase II studies.

603 Background: The safety and efficacy of first-line IRIS (S-1 in combination with irinotecan) and IRIS/Bev (IRIS in combination with bevacizumab [Bev]) have been evaluated in patients with metastatic colorectal cancer (mCRC). To date, no randomized studies comparing these regimens have been performed. This retrospective analysis compared efficacy data for the two regimens from separate phase II studies performed at Hokkaido Gastrointestinal Cancer Study Group (HGCSG). Methods: Patients with histologically confirmed unresectable metastatic or recurrent CRC and received no prior chemotherapy were enrolled. In the first trial, patients received irinotecan 100 mg/m2 on day 1,15 and oral S-1 40 mg/m2 twice daily on days 1-14 every 4 weeks (IRIS study: HGCSG0302). In the second trial, patients received the same regimen plus Bev 5 mg/kg on day 1,15 (IRIS/Bev study). Results: A total of 40 and 52 patients were enrolled the IRIS and IRIS/Bev studies, respectively. Patient characteristics were generally similar i...

Evaluation of usefulness of Royal Marsden Hospital prognostic index in second-line chemotherapy of advanced gastric cancer.

163 Background: Royal Marsden Hospital prognostic Index (RMH-I), which was based on performance status, ALP, liver metastasis and peritoneal metastasis, was reported as prognostic factor of advanced esophago-gastric cancer before first line chemotherapy (Chau I, et al. J Clin Oncol 22:2395-2403, 2004). Usefulness of RMH-I in second line chemotherapy is not elucidated. Methods: Advanced gastric cancer patients who started second line chemotherapy in Hokkaido University Hospital from July 2001 to May 2013 with prior fluoropyrimidine plus platinum administration were retrospectively analyzed. Univariate and multivariate analysis for overall survival were performed using patient characteristics (RMH-I, hemoglobin, CRP, CEA, Alb, TTP in first line, primary lesion resection, and bone metastasis). Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: There were 77 eligible patients. Male/Female were 52/25, median age was 60 years (range 31-80) and u...

Phase II trial of S-1 plus split cisplatin (SSP) in patients with advanced gastric cancer (HGCSG0702): Final report.

113 Background: On the basis of SPIRITS trial, S-1 plus cisplatin has been regarded as standard first-line chemotherapy for patients with advanced gastric cancer (AGC) in Japan (Koizumi W, et al. Lancet Oncol, 2008). However, conventional S-1 plus cisplatin (60mg/m2) regimen requires hospitalization for hydration. Therefore, we conducted phase II trial of S-1 plus split Cisplatin (SSP) for outpatient chemotherapy. Methods: Eligibility criteria included pathologically confirmed AGC; no prior chemotherapy; Age 20 to 75, ECOG performance status (PS) of 0 to 1; adequate organ function; and written informed consent. S-1 (40 mg/m2) was given orally, twice daily for 21 days, and cisplatin (30 mg/m2) was given intravenously on day 1 and 15, followed by 2-week rest period, within a 5-week cycle. Primary endpoint was the response rate (RR), and secondary endpoints were progression-free survival, overall survival, safety profile, and non-hospitalized survival. Results: Between Mar 2008 and Mar 2012, 40 pts were enro...