A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas

TY - JOUR

T1 - A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas

AU - Lassen, Ulrik

AU - Jensen, Lars Henrik

AU - Sorensen, Morten

AU - Rohrberg, Kristoffer S

AU - Ujmajuridze, Zaza

AU - Jakobsen, Anders

PY - 2011/4/1

Y1 - 2011/4/1

N2 - INTRODUCTION: Gemcitabine based regimens have been widely used in patients with advanced cholangiocarcinoma (CC), but no standard therapy exists. In this study we aimed to find the maximally tolerated dose (MTD) of a two-week schedule of fixed dose rate (FDR) gemcitabine (G), oxaliplatin (O) and capecitabine (C), and evaluate the safety and efficacy of this regimen in patients with advanced cholangiocarcinoma (CC).METHODS: In the Phase I part of the study a dose-escalation schedule of FDR G, O and C, administered every two weeks, was performed in patients with solid tumours and no other treatments or advanced CC. In the Phase II part response rate, toxicity, progression-free survival (PFS) and overall survival was evaluated in patients with newly diagnosed advanced CC.RESULTS: Thirty-six patients entered the Phase I part and G 1 000 mg/m(2) day 1 and 15, O 60 mg/m(2) day 1 and 15, and C 1 000 mg/m(2) BID day 1-7 and day 15-21 were established as MTD. In the Phase II part, 41 patients with advanced CC were included. Overall response rate was 34% and 51% had stable disease, resulting in a clinical benefit rate of 85%. Grade III and IV adverse events were rare. Median survival was 12.5 months (95% CI 9.2-15.9) and median progression-free survival (PFS) was 6.9 months (95% CI 5.1-8.6).CONCLUSIONS: This outpatient regimen was very feasible with significant activity and a favourable safety profile. Further studies will explore this combination with addition of newer targeted agents.

AB - INTRODUCTION: Gemcitabine based regimens have been widely used in patients with advanced cholangiocarcinoma (CC), but no standard therapy exists. In this study we aimed to find the maximally tolerated dose (MTD) of a two-week schedule of fixed dose rate (FDR) gemcitabine (G), oxaliplatin (O) and capecitabine (C), and evaluate the safety and efficacy of this regimen in patients with advanced cholangiocarcinoma (CC).METHODS: In the Phase I part of the study a dose-escalation schedule of FDR G, O and C, administered every two weeks, was performed in patients with solid tumours and no other treatments or advanced CC. In the Phase II part response rate, toxicity, progression-free survival (PFS) and overall survival was evaluated in patients with newly diagnosed advanced CC.RESULTS: Thirty-six patients entered the Phase I part and G 1 000 mg/m(2) day 1 and 15, O 60 mg/m(2) day 1 and 15, and C 1 000 mg/m(2) BID day 1-7 and day 15-21 were established as MTD. In the Phase II part, 41 patients with advanced CC were included. Overall response rate was 34% and 51% had stable disease, resulting in a clinical benefit rate of 85%. Grade III and IV adverse events were rare. Median survival was 12.5 months (95% CI 9.2-15.9) and median progression-free survival (PFS) was 6.9 months (95% CI 5.1-8.6).CONCLUSIONS: This outpatient regimen was very feasible with significant activity and a favourable safety profile. Further studies will explore this combination with addition of newer targeted agents.

KW - Adult

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Bile Duct Neoplasms

KW - Bile Ducts, Intrahepatic

KW - Capecitabine

KW - Cholangiocarcinoma

KW - Deoxycytidine

KW - Disease Progression

KW - Dose-Response Relationship, Drug

KW - Drug Administration Schedule

KW - Female

KW - Fluorouracil

KW - Humans

KW - Male

KW - Maximum Tolerated Dose

KW - Middle Aged

KW - Organoplatinum Compounds

KW - Treatment Outcome

KW - Clinical Trial, Phase I

KW - Clinical Trial, Phase II

KW - Journal Article

KW - Multicenter Study

KW - Research Support, Non-U.S. Gov't

U2 - 10.3109/0284186x.2010.500300

DO - 10.3109/0284186x.2010.500300

M3 - Journal article

C2 - 20670085

SN - 1100-1704

VL - 50

SP - 448

EP - 454

JO - Acta Oncologica, Supplement

JF - Acta Oncologica, Supplement

IS - 3

ER -