Prospective Phase II Trial of Gemcitabine in Combination with Irinotecan as First-Line Chemotherapy in Patients with Advanced Biliary Tract Cancer

Institute of Gastroenterology, Yonsei University, Sŏul, Seoul, South Korea
Chemotherapy (Impact Factor: 1.55). 01/2011; 57(3):236-43. DOI: 10.1159/000328021
Source: PubMed

ABSTRACT Chemotherapy is a critical treatment option in advanced biliary tract cancer (BTC), which is often diagnosed at advanced stage and is therefore inoperable. The aim of this phase II trial was to evaluate the efficacy and safety of a combination therapy with gemcitabine and irinotecan as the first-line chemotherapy in patients with previously untreated advanced BTC.
Patients with pathologically confirmed advanced BTC received gemcitabine (1,000 mg/m(2) over 30 min) and irinotecan (100 mg/m(2) over 2 h) on days 1 and 8 every 3 weeks.
Of 39 patients eligible for this trial, 6 had intrahepatic bile duct cancer, 2 had extrahepatic bile duct cancer and 31 had gallbladder cancer. A total of 193 cycles of chemotherapy were administered, with a median of 4 cycles per patient (range 1-18). The objective response rate was 20.5%, and the disease control rate was 66.7% in intention-to-treat analysis. The median progression-free survival was 4.3 months (95% CI 2.70-5.90), and overall survival was 7.6 months (95% CI 4.56-10.64). Grade 3 and 4 toxicities included anemia (20.5% of patients), thrombocytopenia (2.3%), neutropenia (10.3%), aspartate transaminase increase (10.3%), alanine transaminase increase (5.1%) and emesis (5.1%).
Combination therapy of gemcitabine and irinotecan had an efficacy comparable to historic control and can be a viable treatment option. It was well tolerated by patients with advanced BTC.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Gemcitabine (Gem)-based chemotherapies are the main therapeutic regimens for patients with unresectable advanced or metastatic gallbladder cancer (GBC). However, the modest ORR and mild benefit on survival demonstrates the need for finding biomarkers for sensitivity to Gem and hence improving the therapy. In present work, two GBC cell lines with vast difference in sensitivity to Gem were subjected to DNA microarray analysis. Dramatic expression difference was found in protein kinase A signaling, P2Y purigenic receptor signaling, ErbB signaling and p70S6K signaling. Predicted low expression of KRAS and inactivation of AKT/ERK signaling in Gem-resistant GBC cells was validated by quantitative PCR and immunoblotting, respectively. However, p70S6K, p38MAPK and NF-κB signaling was probably activated in Gem-resistant GBC cells, which deserves further investigation in more GBC cell lines and tissues. Our work provides potential pathway signatures for Gem sensitivity of GBC patients.
    International journal of clinical and experimental pathology 01/2014; 7(2):521-8. · 1.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Watch a video presentation of this articleAnswer questions and earn CME
    04/2014; 3(4). DOI:10.1002/cld.337
  • [Show abstract] [Hide abstract]
    ABSTRACT: Leishmaniasis is caused by a parasite of the Leishmania genus, affecting more than 12 million people in 98 countries. The control of leishmaniasis remains a serious problem. There are currently no vaccines for leishmaniasis. The drugs available are toxic, expensive and frequently ineffective. The in vitro activity of SURFACEN® and SP-A against Leishmania amazonensis was evaluated. The combination of both products resulted in a synergic pharmacology effect, demonstrated by a fractional inhibitory concentration index <0.5. A more effective combination was a SURFACEN/SP-A ratio of 4:1, using a method of fixed ratio. The therapeutic effect of SURFACEN and SP-A as antileishmanial compounds was demonstrated, with a potentiation of activity when they were incubated in conjunction. Our results propose an exploration of these products in order to design new formulations against the Leishmania parasite. © 2014 S. Karger AG, Basel.
    Chemotherapy 01/2014; 59(4):247-250. DOI:10.1159/000354771 · 1.55 Impact Factor