gemcitabine and s-1 for advanced biliary tract cancer

Conditions: Biliary Tract Neoplasm

Summary: this study will conduct a phase ii study of gemcitabine and s-1 as first-line chemotherapy in patient with advanced biliary tract cancer

biliary-tract cancer (btc) is invasive carcinoma that originates from the epithelial lining of the gallbladder and bile ducts. btc include cholangiocarcinoma (intrahepatic, perihilar, and distal biliary-tree tumor) and carcinoma arising from the gallbladder. surgical resection of the primary tumor is potentially curative for btc, but less than a quarter of patients are eligible for resection at presentation. systemic chemotherapy is the principal treatment method for patients with unresectable or metastatic btc. gemcitabine is a promising agent, which has shown efficacy in biliary tract cancer. as a single-agent therapy, gemcitabine shows response rates of 8-36% in btc\[4\]. in phase ii trials with patients in advanced btc, gemcitabine in combination with capecitabine or platinum analogues produced objective response rates of 26-50%. the abc-02 study reported a significant survival advantage for gemcitabine and cisplatin over gemcitabine alone in patients with advanced btc (median overall survival 11.7 vs. 8.1 months; p \< 0.001). oral anticancer drug s-1 consists of the 5-fu prodrug tegafur with two biochemical modulators, 5-chloro-2,4-dihydroxypyridine (cdhp) and potassium oxonate (oxo). s-1 monotherapy is active against advanced btc with objective response rates of 21-35%, and phase ii trials of s-1 in combination with gemcitabine reported objective response rates of 20-36%. differences between trials in the doses and administration schedules of gemcitabine and s-1 may be reflected in the ranges of efficacy, dose-intensity, and rates of toxicity observed. even though the efficacy of gemcitabine and s-1 combination is evident for patients with advanced btc in previous phase ii trials, there was no clinical study investigating the efficacy of gemcitabine and s-1 combination for patients with advanced btc when this study was started. therefore, we conducted a phase ii study to evaluate gemcitabine and s-1 combination as first-line chemotherapy for patients with advanced btc.

Eligibility criteria:
inclusion criteria: * unresectable, locally advanced, metastatic adenocarcinoma arising from the intra- and extrahepatic biliary ducts or gallbladder * initially diagnosed or recurred * at least one bidimensionally measurable lesion, defined as at least 1x1cm with clearly defined margins on physical examination, on 3-dimentional ct, mri, or pet-ct * age ≥18 and ≤70 years * estimated life expectancy ≥3 months * ecog performance status ≤2 * adequate bone marrow function (wbcs ≥4,000/µl or absolute neutrophil count ≥1,500/µl, platelets ≥100,000/µl), * adequate kidney function (creatinine ≤1.4 mg/dl) * adequate liver function (bilirubin ≤1.8 mg/dl, transaminase levels ≤100mg/dl) * written informed consent exclusion criteria: * other tumor type than adenocarcinoma * previous history of chemotherapy (exception : adjuvant chemotherapy) * presence of cns metastasis, psychosis, or seizure * obvious bowel obstruction * evidence of serious gastrointestinal bleeding * past or concurrent history of neoplasm other than biliary adenocarcinoma, except for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix uteri * pregnant or lactating women, women of childbearing potential not employing adequate contraception * other serious illness or medical conditions

Keywords: biliary tract neoplasm gemcitabine s-1