A feasibility study of gemcitabine, S-1 and leucovorin combination therapy (GSL) for advanced biliary tract cancer.

Objective: Gemcitabine and cisplatin (GC) combination chemotherapy is the current standard of care for patients with advanced biliary tract cancer (BTC). Recently, a randomized controlled trial showed the non-inferiority in overall survival of gemcitabine and S-1 (GS) compared to GC. Because leucovorin is known to enhance the activity of S-1, we conducted this study to evaluate the feasibility of combination therapy of gemcitabine, S-1 and leucovorin (GSL). Methods: Advanced BTC patients without prior treatment other than surgery or adjuvant chemotherapy were eligible to this study. Gemcitabine was administered at a dose of 1000 mg/m2 on day 1, and oral S-1 at a dose of 40 mg/m2 and oral leucovorin at a dose of 25 mg twice daily on days 1-7, every 2 weeks. The primary endpoint was PFS and the secondary endpoints included OS, objective tumour response and the safety. Results: Between June 2013 and December 2015, 20 patients with advanced BTC (12 gallbladder, 4 extrahepatic, 2 intrahepatic, 2 ampulla) including 16 unresectable disease and 4 recurrent disease were enroled. The median PFS and OS were 5.5 (95% confidence interval [CI], 1.8 - not reached) and 16.0 (95% CI, 6.4-20.8) months, respectively. A partial response was achieved in 3 (15%) and stable disease in 8 (40%), giving a disease control rate of 55%. Major grade 3/4 toxicities included neutropenia (30%), anaemia (5%), stomatitis (15%), diarrhoea (15%) and anorexia (10%). There were no treatment-related deaths. Conclusions: This study showed the feasibility and potential efficacy of GSL as a first-line treatment in patients with advanced BTC.

Efficacy of peppermint oil as an antispasmodic during endoscopic retrograde cholangiopancreatography.

BACKGROUND: During endoscopic retrograde cholangiopancreatography (ERCP), hyoscine-N-butylbromide (Buscopan) or glucagon is used to inhibit duodenal motility. However, they may cause adverse effects. Peppermint oil has an antispasmodic effect and is used as a less hazardous antispasmodic during colonoscopy and upper gastrointestinal endoscopy. The purpose of the present paper was therefore to investigate peppermint as an antispasmodic for ERCP. METHODS: Forty patients were enrolled prospectively. They were assigned to four groups according to the peppermint oil concentration and site of administration: group 1, 20 mL of 1.6% solution around duodenal papilla; group 2, 20 mL of 1.6% solution both to the antrum of the stomach and around the duodenal papilla; group 3, 20 mL of 3.2% solution around the duodenal papilla; and group 4, 3.2% solution both to the antrum and around the duodenal papilla. Glucagon or hyoscine-N-butylbromide was added when duodenal peristalsis was not adequately diminished. Sixteen patients undergoing ERCP with glucagon were employed as historical controls. RESULTS: The ERCP was attempted in all except one patient in group 2 who had bleeding from invaded tumor to the duodenum. Peppermint administration equally reduced duodenal motility in the groups. Duodenal movement was none or mild in 69.2% of patients. The ERCP was successfully performed with peppermint alone in 91.4% of patients (37/39). Glucagon or hyoscine-N-butylbromide was needed in one patient each in groups 1 and 4. Serious complications related to peppermint oil did not occur. Inhibitory effect of peppermint appears to be identical to that of glucagon. CONCLUSION: Duodenal relaxation was obtained with 20 mL of 1.6% peppermint oil solution in the duodenum, but additional administration may be required. Peppermint oil is useful as an antispasmodic agent for ERCP.