Objectives: We assessed the safety and efficacy of docetaxel, a microtubule inhibitor, in patients with advanced hepatocellular carcinoma (HCC). Methods: HCC patients that were not suitable for local therapy, but who possessed measurable disease, good performance status and adequate organ function were eligible. Docetaxel was administered every 3 weeks at a dose of 100 mg/m2 (or 75 mg/m2 if transaminase levels were between 1.5 and 3.5 times the upper normal limit). Efficacy was assessed radiologically every three cycles of chemotherapy. Results: Fifteen patients were enrolled: 11 males and 4 females; their median age was 64 years (range, 42–72 years). Nine patients had underlying cirrhosis. Four patients had been surgically treated before relapse (liver resection in 3 cases and transplantation in 1), 3 had been treated with arterial chemoembolization and 1 with arterial chemotherapy (doxorubicin). A total of 57 cycles of docetaxel were delivered (median 3, range 1–6). Significant toxicity was observed: mostly grade 3–4 neutropenia and fatigue (6 and 4 patients, respectively). Treatment had to be stopped because of toxicity in 6 patients, all having underlying cirrhosis. An important partial response was obtained in 1 patient, a result that enabled liver transplantation; this patient is still alive after 34 months. Five patients had transient stable disease. Conclusion: When used in this schedule, docetaxel does not appear to be safe and effective enough in patients with advanced HCC and cirrhosis.

1.
El-Serag HB: Epidemiology of hepatocellular carcinoma (review). Clin Liver Dis 2001;5:87–107.
2.
Nowak AK, Chow PK, Findlay M: Systemic therapy for advanced hepatocellular carcinoma: a review. Eur J Cancer 2004;40:1474–1484.
3.
Mathurin P, Rixe O, Carbonell N, Bernard B, Cluzel P, Bellin MF, Khayat D, Opolon P, Poynard T: Review article: overview of medical treatments in unresectable hepatocellular carcinoma – an impossible meta-analysis? Aliment Pharmacol Ther 1998;12:111–126.
4.
Coleman RE, Howell A, Eggleton SP, Maling SJ, Miles DW: Phase II study of docetaxel in patients with liver metastases from breast cancer. UK study group. Ann Oncol 2000;11:541–546.
5.
Lin HL, Liu TY, Chau GY, Lui WY, Chi CW: Comparison of 2-methoxyestradiol-induced, docetaxel-induced, and paclitaxel-induced apoptosis in hepatoma cells and its correlation with reactive oxygen species. Cancer 2000;89:983–994.
6.
Zhang H, Ozaki I, Mizuta T, Matsuhashi S, Yoshimura T, Hisatomi A, Tadano J, Sakai T, Yamamoto K: Beta 1-integrin protects hepatoma cells from chemotherapy induced apoptosis via a mitogen-activated protein kinase dependent pathway. Cancer 2002,95:896–906.
7.
Geng CX, Zeng ZC, Wang JY: Docetaxel inhibits SMMC-7721 human hepatocellular carcinoma cells growth and induces apoptosis. World J Gastroenterol 2003;9:696–700.
8.
Sutter AP, Maaser K, Grabowski P, Bradacs G, Vormbrock K, Hopfner M, Krahn A, Heine B, Stein H, Somasundaram R, Schuppan D, Zeitz M, Scherubl H: Peripheral benzodiazepine receptor ligands induce apoptosis and cell cycle arrest in human hepatocellular carcinoma cells and enhance chemosensitivity to paclitaxel, docetaxel, doxorubicin and the Bcl-2 inhibitor HA14-1. J Hepatol 2004;41:799–807.
9.
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205–216.
10.
Olweny CL, Katongole-Mbidde E, Bahendeka S, Otim D, Mugerwa J, Kyalwazi SK: Further experience in treating patients with hepatocellular carcinoma in Uganda. Cancer 1980;46:2717–2722.
11.
Olweny CL, Toya T, Katongole-Mbidde E, Mugerwa J, Kyalwazi SK, Cohen H: Treatment of hepatocellular carcinoma with Adriamycin. Preliminary communication. Cancer 1975;36:1250–1257.
12.
Llovet JM: Updated treatment approach to hepatocellular carcinoma. J Gastroenterol 2005;40:225–235.
13.
O’Reilly EM, Stuart KE, Sanz-Altamira PM, et al: A phase II study of irinotecan in patients with advanced hepatocellular carcinoma. Cancer 2001;91:101–105.
14.
Wall JG, Benedetti JK, O’Rourke MA, Natale RB, Macdonald JS: Phase II trial to topotecan in hepatocellular carcinoma: a Southwest Oncology Group study. Invest New Drugs 1997;15:257–260.
15.
Ulrich-Pur H, Kornek GV, Fiebiger W, Schull B, Raderer M, Scheithauer W: Treatment of advanced hepatocellular carcinoma with biweekly high-dose gemcitabine. Oncology 2001;60:313–315.
16.
Lencioni M, Falcone A, Allegrini G, Pfanner E, Masi G, Brunetti I, Di Marsico R, Fontana E, Orlandini C, Stampino CG, Bartolozzi C, Conte PF: Oral doxifluridine in advanced hepatocellular carcinoma: a phase II study. Oncology 2000;59:204–209.
17.
Chao Y, Chan WK, Birkhofer MJ, Hu OY, Wang SS, Huang YS, Liu M, Whang-Peng J, Chi KH, Lui WY, Lee SD: Phase II and pharmacokinetic study of paclitaxel therapy for unresectable hepatocellular carcinoma patients. Br J Cancer 1998;78:34–39.
18.
Ikeda M, Okusaka T, Ueno H, Takezako Y, Morizane C: A phase II trial of continuous infusion of 5-fluorouracil, mitoxantrone, and cisplatin for metastatic hepatocellular carcinoma. Cancer 2005;103:756–762.
19.
Taieb J, Bonyhay L, Golli L, Ducreux M, Boleslawski E, Tigaud JM, de Baere T, Mansourbakht T, Delgado MA, Hannoun L, Poynard T, Boige V: Gemcitabine plus oxaliplatin for patients with advanced hepatocellular carcinoma using two different schedules. Cancer 2003;98:2664–2670.
20.
Ishikawa T, Ichida T, Yokoyama J, Matsuda Y, Watanabe T, Asakura H: Complete disappearance of pulmonary metastases in a case of hepatocellular carcinoma treated with docetaxel-based systemic chemotherapy. J Gastroenterol Hepatol 2004;19:1423–1426.
21.
Ryan DP, Lynch TJ, Grossbard ML, Seiden MV, Fuchs CS, Grenon N, Baccala P, Berg D, Finkelstein D, Mayer RJ, Clark JW: A phase I study of gemcitabine and docetaxel in patients with metastatic solid tumors. Cancer 2000;88:180–185.
22.
Donelli MG, Zucchetti M, Munzone E, D’Incalci M, Crosignani A: Pharmacokinetics of anticancer agents in patients with impaired liver function. Eur J Cancer 1998;34:33–46.
23.
Clarke SJ, Rivory LP: Clinical pharmacokinetics of docetaxel. Clin Pharmacokinet 1999;36:99–114.
24.
Vogel CL, Bayley AC, Brooker RJ, Anthony PP, Ziegler JL: A phase II study of Adriamycin (NSC 123127) in patients with hepatocellular carcinoma from Zambia and the United States. Cancer 1977;39:1923–1929.
25.
Cusnir M, Patt YZ: Novel systemic therapy options for hepatocellular carcinoma. Cancer J 2004;10:97–103.
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.