美国关于胆管癌临床化疗和试用Erlotinib (Tarceva) 150 mg po qd的报告

Biliary Tract Cancer


Gemcitabine
Gemcitabine (Gemzar) 1000 mg/m2 iv d1, 8
Q3w

Park, JS et al. Single-agent Gemcitabine in the Treatment of Advanced Biliary Tract Cancers: a Phase II Study. Jpn J Clin Oncol 2005; 35:68 (link to the article).

Docetaxel
Docetaxel (Taxotere) 100 mg/m2 iv
Q3w

Papakostas, P et al. First-line chemotherapy with docetaxel for unresectable or metastatic carcinoma of the biliary tract. A multicentre phase II study. Eur J Cancer 2001; 37:1833 (link to the article)
.
Gemcitabine + Capecitabine
Gemcitabine (Gemzar) 1000 mg/m2 iv d1, 8
Capecitabine (Xeloda) 650 mg/m2 po bid d1-14
Q3w

Koeberle D et al. Patient-reported outcomes of patients with advanced biliary tract cancers receiving gemcitabine plus capecitabine: a multicenter, phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol 2008; 26:3702 (link to the article).

Knox, JJ et al. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol 2005; 23:2332 (link to the article).

Gemcitabine + Cisplatin
Gemcitabine (Gemzar) 1250 mg/m2 iv d1, 8
Cisplatin (CDDP) 75 mg/m2 iv d1
Q3w

Thongprasert S et al. Phase II study of gemcitabine and cisplatin as first line chemotherapy in inoperable biliary tract carcinoma. Ann Oncol 2005; 16:279 (link to the article).

Gemcitabine + Oxaliplatin
Gemcitabine (Gemzar) 1000 mg/m2 iv d1
Oxaliplatin (Eloxatin) 100 mg/m2 iv d2
Q2w

Andre, T et al. Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tract adenocarcinoma: a GERCOR study. Ann Oncol 2004; 15:1339 (link to the article)
.
5-FU + Cisplatin
5-FU 1000 mg/m2/d civi d1-5
Cisplatin (CDDP) 100 mg/m2 iv d2
Q3w

Ducreux, M et al. Effective treatment of advanced biliary tract carcinoma using 5-fluorouracil continuous infusion with cisplatin. Ann Oncol 1998; 9:653 (link to the article)
.
LV5FU-P
Leucovorin 200 mg/m2 iv over 2 hrs d1
5-FU 400 mg/m2 iv bolus, followed by 600 mg/m2 iv over 22 hrs, d1 and 2
Cisplatin (CDDP) 50 mg/m2 iv d2
Q2w

Taieb, J et al. Optimization of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of leucovorin, 5-FU and cisplatin (LV5FU2-P regimen) in patients with biliary tract carcinoma. Ann Oncol 2002; 13:1192 (link to the article)

Erlotinib
Erlotinib (Tarceva) 150 mg po qd

Philip PA et al. Phase II study of erlotinib in patients with advanced biliary cancer. J Clin Oncol 2006; 24:3069 (link to the article).

Phase II Study of Erlotinib in Patients With Advanced Biliary Cancer
Philip A. Philip, Michelle R. Mahoney, Cristine Allmer, James Thomas, Henry C. Pitot, George Kim, Ross C. Donehower, Tom Fitch, Joel Picus and Charles Erlichman
+ Author Affiliations

From the Karmanos Cancer Institute, Wayne State University, Detroit, MI; University of Wisconsin Comprehensive Cancer Center, Madison, WI; Howard University College of Medicine, Washington, DC; Bunting Blaustein Cancer Research Bldg, Baltimore, MD; Mayo Clinic Jacksonville, Jacksonville, FL; Mayo Clinic Scottsdale, Scottsdale, AZ; Washington University School of Medicine, St Louis, MO; and the Mayo Clinic, Rochester, MN
Address reprint requests to Philip Agop Philip, MD, PhD, Karmanos Cancer Institute, 4-HWCRC, 4100 John R St, Detroit, MI 48201; e-mail: philipp@karmanos.org
Abstract

Purpose Epidermal growth factor receptor/human epidermal growth factor receptor 1 and ligand expression is common in biliary cancers (BILI) and may be associated with worse outcome. The primary objective of this study was to determine the proportion of patients with advanced BILI who were progression-free at 6 months.

Methods Patients with either unresectable or metastatic disease were studied. Only one prior systemic or locoregional therapy was allowed. Erlotinib was administered continuously at a dose of 150 mg per day orally.

Results Forty-two patients with BILI were enrolled. The median age was 67 years (range, 33 to 82 years). Fifty-two percent of patients had Eastern Cooperative Oncology Group performance status of 1. Fifty-seven percent of patients had received prior chemotherapy for advanced BILI. HER1/EGFR expression by immunohistochemistry in tumor cells was detected in 29 (81%) of the 36 assessable patients. Seven of the patients (17%; 95% CI, 7% to 31%) were progression free at 6 months. Three patients had partial response by Response Evaluation Criteria in Solid Tumors Group classification of duration 4, 4, and 14 months, respectively. All responding patients had mild (grade 1/2) skin rash and two patients had positive tumoral HER1/EGFR expression. Three patients (7%) had toxicity-related dose reductions of erlotinib due to grade 2/3 skin rash.

Conclusion Results suggest a therapeutic benefit for EGFR blockade with erlotinib in patients with biliary cancer. Additional studies with erlotinib as a single agent and in combination with other targeted agents are warranted in this disease.

Footnotes

Supported by Grant No. NO-1 CM17104 from the National Cancer Institute.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Received December 22, 2005.
Accepted April 7, 2006.