Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Dec;85(12):1850–1852. doi: 10.1054/bjoc.2001.2149

Pilot study with pegylated liposomal doxorubicin for advanced or unresectable hepatocellular carcinoma

M Schmidinger 1, C Wenzel 1, G J Locker 1, F Muehlbacher 2, R Steininger 2, M Gnant 2, R Crevenna 3, A C Budinsky 1
PMCID: PMC2364023  PMID: 11747325

Abstract

We performed a pilot-study on pegylated liposomal doxorubicin (PLD) for advanced hepatocellular carcinoma. Seventeen patients received 40 mg/m2 PLD intravenously every 4 weeks. A clinical benefit response was achieved in 50% (complete remission 7%, minor remission 7%, stable disease 36%). Toxicities were moderate. In view of these encouraging findings, further studies appear warranted. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: hepatocellular carcinoma, liposomal doxorubicin, chemotherapy, toxicity, survival

Full Text

The Full Text of this article is available as a PDF (43.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahlgren J. D. Chemotherapy for pancreatic carcinoma. Cancer. 1996 Aug 1;78(3 Suppl):654–663. doi: 10.1002/(SICI)1097-0142(19960801)78:3<654::AID-CNCR46>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
  2. Baas P., van Meerbeeck J., Groen H., Schouwink H., Burgers S., Daamen S., Giaccone G. Caelyx in malignant mesothelioma: a phase II EORTC study. Ann Oncol. 2000 Jun;11(6):697–700. doi: 10.1023/a:1008346925273. [DOI] [PubMed] [Google Scholar]
  3. Beppu T., Ohara C., Yamaguchi Y., Ichihara T., Yamanaka T., Katafuchi S., Ikei S., Mori K., Fukushima S., Nakano M. A new approach to chemoembolization for unresectable hepatocellular carcinoma using aclarubicin microspheres in combination with cisplatin suspended in iodized oil. Cancer. 1991 Dec 15;68(12):2555–2560. doi: 10.1002/1097-0142(19911215)68:12<2555::aid-cncr2820681204>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  4. Burris H. A., 3rd, Moore M. J., Andersen J., Green M. R., Rothenberg M. L., Modiano M. R., Cripps M. C., Portenoy R. K., Storniolo A. M., Tarassoff P. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403–2413. doi: 10.1200/JCO.1997.15.6.2403. [DOI] [PubMed] [Google Scholar]
  5. Falkson G., MacIntyre J. M., Schutt A. J., Coetzer B., Johnson L. A., Simson I. W., Douglass H. O., Jr Neocarzinostatin versus m-AMSA or doxorubicin in hepatocellular carcinoma. J Clin Oncol. 1984 Jun;2(6):581–584. doi: 10.1200/JCO.1984.2.6.581. [DOI] [PubMed] [Google Scholar]
  6. Falkson G., Moertel C. G., Lavin P., Pretorius F. J., Carbone P. P. Chemotherapy studies in primary liver cancer: a prospective randomized clinical trial. Cancer. 1978 Nov;42(5):2149–2156. doi: 10.1002/1097-0142(197811)42:5<2149::aid-cncr2820420510>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  7. Fujimoto S., Miyazaki M., Endoh F., Takahashi O., Okui K., Morimoto Y. Biodegradable mitomycin C microspheres given intra-arterially for inoperable hepatic cancer. With particular reference to a comparison with continuous infusion of mitomycin C and 5-fluorouracil. Cancer. 1985 Nov 15;56(10):2404–2410. doi: 10.1002/1097-0142(19851115)56:10<2404::aid-cncr2820561011>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  8. Gabizon A., Martin F. Polyethylene glycol-coated (pegylated) liposomal doxorubicin. Rationale for use in solid tumours. Drugs. 1997;54 (Suppl 4):15–21. doi: 10.2165/00003495-199700544-00005. [DOI] [PubMed] [Google Scholar]
  9. Gabizon A., Meshorer A., Barenholz Y. Comparative long-term study of the toxicities of free and liposome-associated doxorubicin in mice after intravenous administration. J Natl Cancer Inst. 1986 Aug;77(2):459–469. [PubMed] [Google Scholar]
  10. Gordon A. N., Granai C. O., Rose P. G., Hainsworth J., Lopez A., Weissman C., Rosales R., Sharpington T. Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer. J Clin Oncol. 2000 Sep;18(17):3093–3100. doi: 10.1200/JCO.2000.18.17.3093. [DOI] [PubMed] [Google Scholar]
  11. Halm U., Etzrodt G., Schiefke I., Schmidt F., Witzigmann H., Mössner J., Berr F. A phase II study of pegylated liposomal doxorubicin for treatment of advanced hepatocellular carcinoma. Ann Oncol. 2000 Jan;11(1):113–114. doi: 10.1023/a:1008386822906. [DOI] [PubMed] [Google Scholar]
  12. Hoffman K., Glimelius B. Evaluation of clinical benefit of chemotherapy in patients with upper gastrointestinal cancer. Acta Oncol. 1998;37(7-8):651–659. doi: 10.1080/028418698429991. [DOI] [PubMed] [Google Scholar]
  13. Hong R. L., Tseng Y. L., Chang F. H. Pegylated liposomal doxorubicin in treating a case of advanced hepatocellular carcinoma with severe hepatic dysfunction and pharmacokinetic study. Ann Oncol. 2000 Mar;11(3):349–353. doi: 10.1023/a:1008394125040. [DOI] [PubMed] [Google Scholar]
  14. Judson I., Radford J. A., Harris M., Blay J. Y., van Hoesel Q., le Cesne A., van Oosterom A. T., Clemons M. J., Kamby C., Hermans C. Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2001 May;37(7):870–877. doi: 10.1016/s0959-8049(01)00050-8. [DOI] [PubMed] [Google Scholar]
  15. Konno T., Maeda H., Iwai K., Tashiro S., Maki S., Morinaga T., Mochinaga M., Hiraoka T., Yokoyama I. Effect of arterial administration of high-molecular-weight anticancer agent SMANCS with lipid lymphographic agent on hepatoma: a preliminary report. Eur J Cancer Clin Oncol. 1983 Aug;19(8):1053–1065. doi: 10.1016/0277-5379(83)90028-7. [DOI] [PubMed] [Google Scholar]
  16. Lai C. L., Wu P. C., Chan G. C., Lok A. S., Lin H. J. Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial. Cancer. 1988 Aug 1;62(3):479–483. doi: 10.1002/1097-0142(19880801)62:3<479::aid-cncr2820620306>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  17. Muggia F. M., Hainsworth J. D., Jeffers S., Miller P., Groshen S., Tan M., Roman L., Uziely B., Muderspach L., Garcia A. Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol. 1997 Mar;15(3):987–993. doi: 10.1200/JCO.1997.15.3.987. [DOI] [PubMed] [Google Scholar]
  18. Onohara S., Kobayashi H., Itoh Y., Shinohara S. Intra-arterial cis-platinum infusion with sodium thiosulfate protection and angiotensin II induced hypertension for treatment of hepatocellular carcinoma. Acta Radiol. 1988 Mar-Apr;29(2):197–202. [PubMed] [Google Scholar]
  19. Ranson M. R., Carmichael J., O'Byrne K., Stewart S., Smith D., Howell A. Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial. J Clin Oncol. 1997 Oct;15(10):3185–3191. doi: 10.1200/JCO.1997.15.10.3185. [DOI] [PubMed] [Google Scholar]
  20. Sasaki Y., Imaoka S., Kasugai H., Fujita M., Kawamoto S., Ishiguro S., Kojima J., Ishikawa O., Ohigashi H., Furukawa H. A new approach to chemoembolization therapy for hepatoma using ethiodized oil, cisplatin, and gelatin sponge. Cancer. 1987 Sep 15;60(6):1194–1203. doi: 10.1002/1097-0142(19870915)60:6<1194::aid-cncr2820600607>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  21. Scheithauer W., Kornek G. V., Raderer M., Hejna M., Valencak J., Miholic J., Kovats E., Lang F., Funovics J., Bareck E. Phase II trial of gemcitabine, epirubicin and granulocyte colony-stimulating factor in patients with advanced pancreatic adenocarcinoma. Br J Cancer. 1999 Aug;80(11):1797–1802. doi: 10.1038/sj.bjc.6690600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schöniger-Hekele M., Müller C., Kutilek M., Oesterreicher C., Ferenci P., Gangl A. Hepatocellular carcinoma in Central Europe: prognostic features and survival. Gut. 2001 Jan;48(1):103–109. doi: 10.1136/gut.48.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Simonetti R. G., Liberati A., Angiolini C., Pagliaro L. Treatment of hepatocellular carcinoma: a systematic review of randomized controlled trials. Ann Oncol. 1997 Feb;8(2):117–136. doi: 10.1023/a:1008285123736. [DOI] [PubMed] [Google Scholar]
  24. Toma S., Tucci A., Villani G., Carteni G., Spadini N., Palumbo R. Liposomal doxorubicin (Caelyx) in advanced pretreated soft tissue sarcomas: a phase II study of the Italian Sarcoma Group (ISG). Anticancer Res. 2000 Jan-Feb;20(1B):485–491. [PubMed] [Google Scholar]
  25. Zou Y., Horikoshi I., Kasagi T., Gu X., Perez-Soler R. Organ distribution and antitumor activity of free and liposomal doxorubicin injected into the hepatic artery. Cancer Chemother Pharmacol. 1993;31(4):313–318. doi: 10.1007/BF00685677. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES