Objective: To clarify the role of chemotherapy for advanced gallbladder cancer (GBC). Methods: We reviewed 89 GBC patients: 21 admitted before 1997 were treated with a combination of cisplatin, epirubicin, and 5-fluorouracil (CEF); 25, admitted subsequently, received a combination of 5-fluorouracil, doxorubicin and mitomycin (FAM), and the remaining 43, ineligible for these trials, received supportive care. We investigated the relation between pretreatment clinical variables and long-term survival in these 89 subjects, and analyzed whether chemotherapy could favor longer survival. Results: There were no significant differences in survival time between the chemotherapy groups, whereas the response rate to the CEF regimen was 4-fold higher than to the FAM regimen (32 vs. 8%). Subgroup analysis suggested that chemotherapy favored longer survival in patients with a performance status (PS) of 0 or 1, but not in patients with a PS of 2. Cox regression analysis suggested a significant hazard reduction by chemotherapy in patients with a PS of 0 or 1, but not in patients with a PS of 2. Conclusions: GBC patients with poor PS should not be treated with chemotherapy at present. It is essential to design good clinical trials and develop more effective chemotherapy regimens.

Keywords:
Gallbladder cancer, Biliary tract neoplasm, Chemotherapy, Clinical trial, Prognosis
1.
Anonymous: The editorial board of the cancer statistics in Japan. Cancer statistics in Japan 2001. Tokyo, Foundation for Promotion of Cancer Research, 2001.
2.
Harvey JH, Smith FP, Schein PS: 5-fluorouracil, mitomycin, and doxorubicin (FAM) in carcinoma of the biliary tract. J Clin Oncol 1984;2:1245–1248.
3.
Taal BG, Audisio RA, Bleiberg H, Blijham GH, Neijt JP, Veenhof CH, Duez N, Sahmoud T: Phase II trial of mitomycin C in advanced gallbladder and biliary tree carcinoma. An EORTC Gastrointestinal Tract Cooperative Group Study. Ann Oncol 1993;4:607–609.
4.
Okada S, Ishii H, Nose H, Yoshimori M, Okusaka T, Aoki K, Iwasaki M, Furuse J, Yoshino M: A phase II study of cisplatin in patients with biliary tract carcinoma. Oncology 1994;51:515–517.
5.
Patt YZ, Jones DV Jr, Hoque A, Lozano R, Markowitz A, Raijman I, Lynch P, Charnsangavej C: Phase II trial of intravenous fluorouracil and subcutaneous interferon alfa-2b for biliary tract cancer. J Clin Oncol 1996;14:2311–2315.
6.
Jones DV Jr, Lozano R, Hoque A, Markowitz A, Patt YZ: Phase II study of paclitaxel therapy for unresectable biliary tree carcinomas. J Clin Oncol 1996;14:2306–2310.
7.
Sanz-Altamira PM, Ferrante K, Jenkins RL, Lewis WD, Huberman MS, Stuart KE: A phase II trial of 5-fluorouracil, leucovorin, and carboplatin in patients with unresectable biliary tract carcinoma. Cancer 1998;82:2321–2325.
8.
Pazdur R, Royce ME, Rodriguez GI, Rinaldi DA, Patt YZ, Hoff PM, Burris HA: Phase II trial of docetaxel for cholangiocarcinoma. Am J Clin Oncol 1999;22:78–81.
9.
Penz M, Kornek GV, Raderer M, Ulrich-Pur H, Fiebiger W, Lenauer A, Depisch D, Krauss G, Schneeweiss B, Scheithauer W: Phase II trial of two-weekly gemcitabine in patients with advanced biliary tract cancer. Ann Oncol 2001;12:183–186.
10.
Patt YZ, Hassan MM, Lozano RD, Waugh KA, Hoque AM, Frome AI, Lahoti S, Ellis L, Vauthey JN, Curley SA, Schnirer II, Raijman I: Phase II trial of cisplatin, interferon alpha-2b, doxorubicin, and 5-fluorouracil for biliary tract cancer. Clin Cancer Res 2001;7:3375–3380.
11.
World Health Organization: WHO Handbook for Reporting Results of Cancer Treatment. Offset publication 48. Geneva, World Health Organization, 1979.
12.
Sobin L, Wittekind C: TNM Classification of Malignant Tumours, ed 5. John Wiley & Sons, New York, 1997.
13.
Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;63:457–481.
14.
Cox DR: Regression models and life-tables [with discussion]. J R Stat Soc 1972;34[series B]:187–220.
15.
Percy C, Van Holten V, Muir C (eds): International classification of diseases for oncology, ed 5. Geneva, World Health Organization, 1990.
16.
Ellis PA, Norman A, Hill A, O’Brien ME, Nicolson M, Hickish T, Cunningham D: Epirubicin, cisplatin and infusional 5-fluorouracil (5-FU) (ECF) in hepatobiliary tumours. Eur J Cancer 1995;10:1594–1598.
17.
Okada S, Okazaki N, Nose H, Yoshimori M, Aoki K: Prognostic factors in patients with hepatocellular carcinoma receiving systemic chemotherapy. Hepatology 1992;16:112–117.
18.
Shinkai T, Eguchi K, Sasaki Y, Tamura T, Ohe Y, Kojima A, Oshita F, Miya T, Okamoto H, Iemura K, Saijo N: A prognostic-factor risk index in advanced non-small-cell lung cancer treated with cisplatin-containing combination chemotherapy. Cancer Chemother Pharmacol 1992;30:1–6.
19.
Ishii H, Okada S, Nose H, Yoshimori M, Aoki K, Okusaka T: Prognostic factors in patients with advanced pancreatic cancer treated with systemic chemotherapy. Pancreas 1996;12:267–271.
© 2004 S. Karger AG, Basel
2004
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.