Gemcitabine, oxaliplatin and 5-FU in advanced bile duct and gallbladder carcinoma: two parallel, multicentre phase-II trials

Abstract

BACKGROUND: Gemcitabine, oxaliplatin and 5-fluorouracil (5-FU) are active in biliary tract cancer and have a potentially synergistic mode of action and non-overlapping toxicity. The objective of these trials was to determine response, survival and toxicity separately in patients with bile duct cancer (BDC) and gallbladder cancer (GBC) treated with gemcitabine/oxaliplatin/5-FU chemotherapy. METHODS: Eligible patients with histologically proven, advanced or metastatic BDC (n ¼ 37) or GBC (n ¼ 35) were treated with gemcitabine (900 mg m À2 over 30 min), oxaliplatin (65 mg m À2 ) and 5-FU (1500 mg m À2 over 24 h) on days 1 and 8 of a 21-day cycle. Tumour response was the primary outcome measure. RESULTS: Response rates were 19% (95% CI: 6 -32%) and 23% (95% CI: 9 -37%) for BDC and GBC, respectively. Median survivals were 10.0 months (95% CI: 8.6 -12.4) and 9.9 months (95% CI: 7.5 -12.2) for BDC and GBC, respectively, and 1-and 2-year survival rates were 40 and 23% in BDC and 34 and 6% in GBC (intention-to-treat analysis). Major grade III and IV adverse events were neutropenia, thrombocytopenia, elevated bilirubin and anorexia. CONCLUSION: Triple-drug chemotherapy achieves comparable results for response and survival to previously reported regimens, but with more toxicity.

Synergic effect of photodynamic therapy using talaporfin sodium with conventional anticancer chemotherapy for the treatment of bile duct carcinoma

“…27 Chemotherapy alone using novel anticancer drugs did not show an acceptable survival period (the median overall survival was 4.7-15.4 months), and the tumor response rate was 9-37% (median progression free survival was 3-7.2 months). [28][29][30][31][32][33][34][35] In Japan, gemcitabine has been mainly used to treat bile duct carcinoma and is now a key drug in the treatment of bile duct carcinoma. 36,37 Previous our studies using cultured cells showed that the main effect of PDT is apoptosis, evidenced by assays that measured either DNA fragmentation or chromatin condensation.…”

Randomized phase II study of gemcitabine plus S‐1 versus S‐1 in advanced biliary tract cancer: A Japan Clinical Oncology Group trial (JCOG 0805)

“…(8,(14)(15)(16)(17) Another stratification factor used in this study was the clinical stage (II or III versus IV or recurrent). Locally advanced or metastatic cancer, the stratification factor used in the ABC-01 and ABC-02 studies, (7,18) has been shown to affect the OS of patients with advanced BTC.…”

Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma

“…However, no standard chemotherapy regimen for advanced BTC has been established. Several phase II trials with new chemotherapeutic agents, such as gemcitabine (6)(7)(8)(9)(10), capecitabine (11), oxaliplatin (12), or S-1 (13,14) have demonstrated tumor response in ~15-35% of patients treated with single agents, and in 20-40% of patients treated with their combinations (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Among them, gemcitabine has shown promising activity against advanced BTC, and has been commonly used for patients with unresectable or recurrent BTC in Japan.…”