Kensaku Yoshida

Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05)

BACKGROUND In Japan, S-1 plus cisplatin has been used as first-line therapy for advanced gastric cancer (AGC). Patients with no response to first-line treatment with S-1 often receive a taxane-alone or irinotecan-alone as second-line treatment. However, second-line treatment with S-1 plus irinotecan is widely used in patients with AGC resistant to first-line S-1-based chemotherapy. The goal of this trial was to determine whether the consecutive use of S-1 plus irinotecan improves survival when compared with irinotecan-alone as second-line treatment for AGC. PATIENTS AND METHODS Patients who had disease progression during first-line S-1-based chemotherapy were randomly assigned to receive S-1 plus irinotecan or irinotecan-alone. The S-1 plus irinotecan group received oral S-1 (40-60 mg/m(2)) on days 1-14 and intravenous irinotecan (150 mg/m(2)) on day 1 of a 21-day cycle. The irinotecan-alone group received the same dose of irinotecan intravenously on day 1 of a 14-day cycle. The primary end point was overall survival (OS). RESULTS From February 2008 to May 2011, a total of 304 patients were enrolled. The median OS was 8.8 months in the S-1 plus irinotecan group and 9.5 months in the irinotecan-alone group. This difference was not significant (hazard ratio for death, 0.99; 95% confidence interval 0.78-1.25; P = 0.92). Grade 3 or higher toxicities were more common in the S-1 plus irinotecan group than in the irinotecan-alone group. CONCLUSION The consecutive use of S-1 plus irinotecan is not recommended as second-line treatment in patients who are refractory to S-1-based first-line chemotherapy. ClinicalTrials.gov ID: NCT00639327.

A multicenter prospective phase II study of first-line modified FOLFIRINOX for unresectable advanced pancreatic cancer

Background FOLFIRINOX (FX) has been reported as an effective treatment for unresectable advanced pancreatic cancer. However, FX is associated with a high incidence of adverse events (AEs). A previous phase II study in Japan showed high incidences of hematological AEs, including febrile neutropenia (22.2%). A modified FX regimen (mFX) may decrease the rates of AEs and be more effective than FX by improving the treatment compliance. Aims To assess the safety and efficacy of first-line mFX for unresectable advanced pancreatic cancer. Patients and methods This was as a multicenter prospective phase II study in chemotherapy-naïve Japanese patients with pathologically confirmed unresectable advanced pancreatic adenocarcinoma or adenosquamous carcinoma. Treatment with mFX (85 mg/m2 oxaliplatin, 150 mg/m2 irinotecan, and 200 mg/m2 l-leucovorin, followed by 46-h continuous infusion of 2400 mg/m2 5-fluorouracil) was administered every 2 weeks. The primary endpoint was the response rate. The secondary endpoints were overall survival, progression-free survival, and safety. Results Thirty-one patients (18 men; median age, 64 years) were enrolled. A median of 13 treatment cycles were administered during a median follow-up period of 14.2 months. The response rate, median overall survival, and median progression-free survival were 38.7%, 14.9 months, and 7.0 months, respectively. Grade 3 or 4 AEs included neutropenia (83.9%), febrile neutropenia (16.1%), peripheral sensory neuropathy (9.7%), thrombocytopenia (6.5%), diarrhea (6.5%), anorexia (6.5%), and vomiting (3.2%). Conclusion Compared to FX, mFX may result in fewer Grade 3 or 4 non-hematological AEs, with a comparable response rate. However, further efforts might be required to reduce hematological AEs.

EUS-guided hybrid rendezvous technique as salvage for standard rendezvous with intra-hepatic bile duct approach

EUS-guided rendezvous technique (EUS-RV) is an effective salvage technique for failed biliary cannulation during ERCP. However, it is still difficult to achieve cannulation in some cases, especially using the intrahepatic bile duct (IHBD) approach, which requires complicated guidewire manipulation. EUS-hybrid rendezvous technique (HRV) has been applied as a salvage technique for difficult guidewire placement during EUS-RV with IHBD approach. The aims of this study were to evaluate the efficacy and safety of EUS-HRV using a retrospective study. Database analysis revealed 29 patients who underwent EUS-RV for difficult biliary cannulation. Among them, 8 patients underwent EUS-HRV as a salvage technique for difficult guidewire placement during EUS-RV with the IHBD approach. In EUS-HRV, a 6-French dilator was advanced into the biliary system for better guidewire manipulation. After successful guidewire placement, the EUS scope was exchanged for a duodenoscope, keeping the guidewire and dilator in place. The EUS-placed guidewire was retrieved through the duodenoscope, followed by cannulation over the guidewire. The dilator remained at the fistula until completion of the procedure. The analysis showed that the guidewire placement and the subsequent scope exchange and deep biliary cannulation after the retrieval of the EUS-placed guidewire were successfully conducted for all 8 patients. Mild pancreatitis was recognized as an adverse event in 1 patient. The overall success rate of EUS-RV combined with EUS-HRV was improved up to 90% (26/29). Our results suggested that EUS-HRV can be an effective and safe salvage technique in cases wherein guidewire placement is difficult during EUS-RV with IHBD approach.

Comparison of late adverse events after endoscopic sphincterotomy versus endoscopic papillary large balloon dilation for common bile duct stones: A propensity score‐based cohort analysis

Endoscopic sphincterotomy (ES) is a standard procedure for the treatment of common bile duct stones (CBDS). Endoscopic papillary large balloon dilation (EPLBD) is emerging as an effective method to treat difficult CBDS, providing several advantages over ES without increasing early adverse events (AE). However, the late AE of EPLBD have not yet been well studied. The aim of the present study was to compare late AE after EPLBD versus ES for the treatment of CBDS using a propensity score‐based cohort analysis.

O2-16-2Phase 2 study of 1st-line modified FOLFIRINOX in unresectable advanced pancreatic cancer: Multicenter prospective study

Hideyuki Hayashi, Shigeki Tanishima, Ryo Mori, Yasunobu Okamura, Toraji Amano, Ichiro Kinoshita, Yoshito Komatsu, Hirotoshi Dosaka-akita, Hiroshi Nishihara Division of Clinical Cancer Genomics, Hokkaido University Hospital, Department of Biomedical Informatics Development, Mitsubishi Space Software Co., Ltd, Hokkaido University Hospital Clinical Research and Medical Innovation Center, Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center