Phase II study of gemcitabine, oxaliplatin in combination with panitumumab in KRAS wild-type unresectable or metastatic biliary tract and gallbladder cancer

被引：53

作者：

Hezel, A. F. ^{[1
]}

Noel, M. S. ^{[1
]}

Allen, J. N. ^{[2
]}

Abrams, T. A. ^{[3
]}

Yurgelun, M. ^{[3
]}

Faris, J. E. ^{[2
]}

Goyal, L. ^{[2
]}

Clark, J. W. ^{[2
]}

Blaszkowsky, L. S. ^{[2
]}

Murphy, J. E. ^{[2
]}

Zheng, H. ^{[4
]}

Khorana, A. A. ^{[5
]}

Connolly, G. C. ^{[1
]}

Hyrien, O. ^{[6
]}

Baran, A. ^{[6
]}

Herr, M. ^{[7
]}

Ng, K. ^{[3
]}

Sheehan, S. ^{[2
]}

Harris, D. J. ^{[2
]}

Regan, E. ^{[3
]}

Borger, D. R. ^{[8
]}

Iafrate, A. J. ^{[8
]}

Fuchs, C. ^{[3
]}

Ryan, D. P. ^{[2
]}

Zhu, A. X. ^{[2
]}

机构：

[1] Univ Rochester, James P Wilmot Canc Ctr, Div Hematol Oncol, Rochester, NY 14642 USA

[2] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA

[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[4] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA

[5] Cleveland Clin Fdn, Taussig Canc Inst, Cleveland, OH 44195 USA

[6] Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA

[7] Univ Rochester, Med Ctr, Dept Publ Hlth Sci, Rochester, NY 14642 USA

[8] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

来源：

BRITISH JOURNAL OF CANCER | 2014年 / 111卷 / 03期

关键词：

biliary tract cancer; cholangiocarcinoma; epidermal growth factor receptor EGFR; KRAS; panitumumab; TARGETED THERAPY; K-RAS; CHOLANGIOCARCINOMA; TRIAL; CHEMOTHERAPY; ERLOTINIB; EGFR; MULTICENTER; EXPRESSION; CETUXIMAB;

D O I：

10.1038/bjc.2014.343

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Current data suggest that platinum-based combination therapy is the standard first-line treatment for biliary tract cancer. EGFR inhibition has proven beneficial across a number of gastrointestinal malignancies; and has shown specific advantages among KRAS wild-type genetic subtypes of colon cancer. We report the combination of panitumumab with gemcitabine (GEM) and oxaliplatin (OX) as first-line therapy for KRAS wild-type biliary tract cancer. Methods: Patients with histologically confirmed, previously untreated, unresectable or metastatic KRAS wild-type biliary tract or gallbladder adenocarcinoma with ECOG performance status 0-2 were treated with panitumumab 6mgkg(-1), GEM 1000 mgm(-2) (10 mgm(-2) min(-1)) and OX 85 mgm(-2) on days 1 and 15 of each 28-day cycle. The primary objective was to determine the objective response rate by RECIST criteria v.1.1. Secondary objectives were to evaluate toxicity, progression-free survival (PFS), and overall survival. Results: Thirty-one patients received at least one cycle of treatment across three institutions, 28 had measurable disease. Response rate was 45% and disease control rate was 90%. Median PFS was 10.6 months (95% CI 5-24 months) and median overall survival 20.3 months (95% CI 9-25 months). The most common grade 3/4 adverse events were anaemia 26%, leukopenia 23%, fatigue 23%, neuropathy 16% and rash 10%. Conclusions: The combination of gemcitabine, oxaliplatin and panitumumab in KRAS wild type metastatic biliary tract cancer showed encouraging efficacy, additional efforts of genetic stratification and targeted therapy is warranted in biliary tract cancer.

引用

页码：430 / 436

页数：7

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