A Phase II Study of Gemcitabine and TS-1 in Patients With Previously Untreated Metastatic or Recurrent Biliary Tract Cancer
At present, surgery is the only curative treatment option for biliary tract cancer (BTC).
However, less than 25% of patients are resectable at presentation with high relapse rates
after surgery. Because of the low incidence and heterogeneity of BTC, clinical trials are
difficult to conduct in these patients, hampering the evaluation of optimal chemotherapy
regimens. Owing to the lack of randomized phase III studies, there is no standard regimen
for palliative chemotherapy of GBC and CC. But the exploration of an optimal regimen for
standard first-line chemotherapy for BTC is imperative in order to improve survival in these
Gemcitabine has demonstrated antitumor activity as monotherapy in phase II trials in BTC
patients with response rates ranging from 22 to 36% (2001 Proc Am Soc Clin Oncol 20:A626,
2001 J Clin Oncol 19(20):4089-4091, 2001 Ann Oncol 12(2):183-186).
As with most gastrointestinal tumors, 5-fluorouracil (5-FU) is the most studied drug as a
single agent or a combination in different dosages and schedules with response rates of
10-20% and with median survival of 7-9 months in BTC (2005 Cancer 103:111-118, 2001 Clin
Cancer Res 7:3375-3380).
The combination of gemcitabine and fluoropyrimidine in biliary cancers is worthy of further
evaluation. The toxicity profiles of these agents are known to be non-overlapping, and
combinations have been well tolerated. Oral fluoropyrimidines are considered to be an
alternative to conventional protracted 5-FU infusion as far as they provide comparable
efficacy and compliance.
S-1 is oral fluoropyrimidine preparation developed by Taiho Pharmaceutical Co., Ltd. (Tokyo,
Japan) that combines tegafur with two 5-FU modulators, 5-chloro-2, 4-dihydroxypyridine
(CDHP) and potassium oxonate (Oxo), in a molar ratio of 1:0.4:1. Tegafur, a prodrug of 5-FU,
is converted to 5-FU mainly in liver and tumor cells. CDHP, a reversible inhibitor of
dihydropyrimidine dehydrogenase, suppresses the degradation of 5-FU, thereby maintaining
high concentrations of 5-FU in plasma and tumor cells. CDHP also decreases cardiotoxic and
neurotoxic effects by reducing the production of F-b-alanine (FBAL), the main catabolite of
5-FU. Several phase II trials showed that TS-1 monotherapy or combination with CDDP,
paclitaxel or irinotecan was effective palliative treatment option for advanced gastric
cancer and colorectal cancer.
In current study, we evaluate the efficacy of gemcitabine and TS-1 combination chemotherapy
in advanced BTC.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Korea: Food and Drug Administration