Format

Send to:

Choose Destination
See comment in PubMed Commons below
Oncotarget. 2013 Jan 27;4(1):153-62. Print 2013 Jan.

Targeted therapy of advanced gallbladder cancer and cholangiocarcinoma with aggressive biology: eliciting early response signals from phase 1 trials.

Author information

  • 1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. isubbiah@mdanderson.org

Abstract

PURPOSE:

Patients with advanced cholangiocarcinoma (CC) and gallbladder carcinoma (GC) have few therapeutic options for relapsed disease.

METHODS:

Given the overall poor prognosis in this population and the availability of novel targeted therapies, we systematically analyzed the characteristics and outcomes for GC and CC patients treated on phase I trials with an emphasis on targeted agents and locoregional therapies.

RESULTS:

Of 40 treated patients (GC=6; CC=34; median age, 60 years), 8 (20%) had stable disease (SD) > 6 months, 3 (8%) partial response (PR), on protocols with hepatic arterial drug infusion and anti-angiogenic, anti-HER-2/neu or novel MAPK/ERK kinase (MEK) inhibitors. Median progression-free survival (PFS) on phase I trials was 2.0 months (95% CI 1.7, 2.8) versus 3.0 months (95% CI 2.4, 5.0), 3.0 months (95% CI 2.3, 4.6), and 3.0 months (95% CI 2.4, 3.9) for their first-, second-, and last-line FDA-approved therapy. In univariate analysis, >3 metastatic sites, elevated alanine aminotransferase (ALT) (>56IU/L), serum creatinine (>1.6mg/dL), and CA19-9 (>35U/mL) were associated with a shorter PFS. Mutational analysis revealed mutation in the KRAS oncogene in 2 of 11 patients (18%). The SD >6 months/PR rate of 28% was seen with hepatic arterial infusion of oxaliplatin, and inhibitors of angiogenesis, HER-2/neu or MEK.

CONCLUSIONS:

The PFS in phase I trials was similar to that of the first, second, and last-line therapy (P=0.95, 0.98, 0.76, respectively) with FDA-approved agents given in the advanced setting, emphasizing a role for targeted agents in a clinical trials setting as potentially valuable therapeutic options for these patients.

KEYWORDS:

cholangiocarcinoma; gallbladder carcinoma; locoregional therapy; phase I; targeted therapy

PMID:
23847722
[PubMed - indexed for MEDLINE]
PMCID:
PMC3702215
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Write to the Help Desk