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Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma

  1. Lyndsay Harris M.D.1,2,†,*,
  2. Gerald Batist M.D.3,
  3. Robert Belt M.D.4,
  4. Douglas Rovira M.D.5,
  5. Rudolph Navari M.D.6,
  6. Nozar Azarnia Ph.D.7,‡,
  7. Lauri Welles M.D.8,§,
  8. Eric Winer M.D.1,2,¶,
  9. TLC D-99 Study Group ‖

Article first published online: 28 DEC 2001

DOI: 10.1002/cncr.10201

Issue

Cancer

Cancer

Volume 94, Issue 1, pages 25–36, 1 January 2002

Additional Information

How to Cite

Harris, L., Batist, G., Belt, R., Rovira, D., Navari, R., Azarnia, N., Welles, L., Winer, E. and TLC D-99 Study Group (2002), Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma. Cancer, 94: 25–36. doi: 10.1002/cncr.10201

Author Information

  1. 1

    Duke University Medical Center, Durham, North Carolina

  2. 2

    Dana-Farber Cancer Institute, Boston, Massachusetts

  3. 3

    McGill University, Montreal, Quebec, Canada

  4. 4

    St. Luke's Hospital, Kansas City, Missouri

  5. 5

    University of Colorado, Denver, Colorado

  6. 6

    Simon Williamson Clinic, Birmingham, Alabama

  7. 7

    Columbia Presbyterian Medical Center, New York, New York

  8. 8

    Elan Pharmaceuticals, Princeton, New Jersey

  1. †

    Fax: (617) 632-3709

  2. ‡

    Dr. Nozar Azarnia is a consultant for Elan Corporation.

  3. §

    Lauri Welles is an employee of Elan Pharmaceuticals.

  4. Eric Winer was a consultant to the Liposome Company in 1999 during the course of their submission of TLD to the FDA.

  5. ‖

    The following investigators and their institutions also participated in the study: Thomas Garrett, Columbia-Presbyterian Medical Center, New York, NY; Douglas Blayney, Lewis Cancer Care Center, Pomona, CA; Laurence Elias, UNM Cancer Center, Albuquerque, NM; Joanne Mortimer, Barnard Cancer Center, St. Louis, MO; Burton Needles, Saint John's Mercy Medical Center, St. Louis, MO; Timothy Webb, Central Arkansas Oncology Clinic, Hot Springs, AR; Joshua Atiba, UC Irvine Medical Center, Orange, CA; John Bickers, LSU Medical Center, New Orleans, LA; Thomas Godfrey, Loma Linda University Medical Center, Loma Linda, CA; Richard Love, University of Wisconsin Hospital, Madison, WI; Dustan Osborn, Western Washington Cancer Center, Olympia, WA; Joseph Aisner, University of Maryland Cancer Center, Baltimore, MD; Tom Anderson, Froedtert Memorial Lutheran Hosp, Milwaukee, WI; Dean Butler, Dial Research Associates, Nashville, TN; Paul Calabresi, Rhode Island Hospital, Providence, RI; Lawrence Feldman, Mount Sinai Hospital, Chicago, IL; Robert Kerr, Southwest Regional Cancer Centers, Austin, TX; Hans Nevinny, Memorial Medical Center, Tulsa, OK; Craig Reynolds, Ocala Oncology Center, Ocala, FL; Andrew Schneider, Hematology and Medical Oncology, Lauderhill, FL; Charles Tweedy, Amos Community Cancer Center, Columbus, GA; William Whaley, West Paces Ferry Clinic, Atlanta, GA; Michael DeMattia, Mount Clemons Hospital, Mount Clemons, MI; Gregory Harper, Lehigh Valley Hospital, Allentown, PA; Rebecca Moroose, Walt Disney Memorial Cancer Institute, Orlando, FL; Harry Staszewski, Winthrop University Hospital, Mineola, NY; Albert Begas, Boca Raton Community Hospital, Boca Raton, FL; Janice Dutcher, Montefiore Medical Center, Bronx, NY; Robert Ellis, Madigan Army Medical Center, Tacoma, WA; Gini Fleming, University of Chicago Medical Center, Chicago, IL; Michael Garcia, Norwood Clinic Research Center, Birmingham, AL; Joel Granick, Midwestern Regional Medical Center, Zion, IL; Jonathan Kloss, Lourdes Hospital Cancer Center, Binghamton, NY; Michael Roberts, Hematology and Oncology Associates, Phoenix, AZ; Federico Sanchez, Cancer Care Center, Menomonee Falls, WI; Richard Silver, New York Hospital–Cornell Medical Center, New York; Harvey Taylor, Hodges Cancer Center, Lubbock, TX.

*Dana-Farber Cancer Institute, Room D1210, 44 Binney Street, Boston, MA 02115

Publication History

  1. Issue published online: 28 DEC 2001
  2. Article first published online: 28 DEC 2001
  3. Manuscript Accepted: 17 AUG 2001
  4. Manuscript Received: 1 JUN 2001

Funded by

  • Elan Pharmaceuticals, Princeton, New Jersey

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REFERENCES

  • 1
    Henderson IC, Allegra JC, Woodcock T, Wolff S, Bryan S, Cartwright K, et al. Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer. J Clin Oncol 1989; 7: 560–71.
  • 2
    Cowan JD, Neidhart J, McClure S, Coltman CA Jr., Gumbart C, Martino S, et al. Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer. J Natl Cancer Inst 1991;83: 1077–84.
  • 3
    Chan S, Friedrichs K, Noel D, Pinter T, Van Belle S, Vorobiof D, et al. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol 1999; 17: 2341–54.
  • 4
    Paridaens R, Biganzoli L, Bruning P, Klijn JG, Gamucci T, Houston S, et al. Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer. J Clin Oncol 2000; 18: 724–33.
  • 5
    Norris B, Pritchard KI, James K, Myles J, Bennett K, Marlin S, et al. Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer. J Clin Oncol 2000; 18: 2385–94.
  • 6
    The French Epirubicin Study Group. A prospective randomized phase III trial comparing combination chemotherapy with cyclophosphamide, fluorouracil, and either doxorubicin or epirubicin. J Clin Oncol 1988;6: 679–88.
  • 7
    The Italian Multicentre Breast Study with Epirubicin. Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer. J Clin Oncol 1988; 6: 976–82.
  • 8
    Bennett JM, Muss HB, Doroshow JH, Wolff S, Krementz ET, Cartwright K, et al. A randomized multicenter trial comparing mitoxantrone, cyclophosphamide, and fluorouracil with doxorubicin, cyclophosphamide, and fluorouracil in the therapy of metastatic breast carcinoma. J Clin Oncol 1988; 6: 1611–20.
  • 9
    Swain SM, Whaley FS, Gerber MC, Weisberg S, York M, Spicer D, et al. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol 1997; 15: 1318–32.
  • 10
    Harris LN, Yang L, Liotcheva V, Pauli S, Iglehart JD, Colvin OM, et al. Induction of topoisomerase II activity after ErbB2 activation is associated with a differential response to breast cancer chemotherapy. Clin Cancer Res 2001; 7: 1497–504.
  • 11
    Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344: 783–92.
  • 12
    Praga C, Beretta G, Vigo PL, Lenaz GR, Pollini C, Bonadonna G, et al. Adriamycin cardiotoxicity. Cancer Treat Rep 1979; 63: 827–34.
  • 13
    Von Hoff DD, Layard MW, Basa P, Davis HL Jr., Von Hoff AL, Rozencweig M, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 1979;91: 710–7.
  • 14
    Schwartz RG, McKenzie WB, Alexander J, Sager P, D'Souza A, Manatunga A, et al. Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Am J Med 1987; 82: 1109–18.
  • 15
    Billingham ME, Mason JW, Bristow MR, Daniels JR. Anthracycline cardiomyopathy monitored by morphologic changes. Cancer Treat Rep 1978; 62: 865–72.
  • 16
    Balazsovits JA, Mayer LD, Bally MB, Cullis PR, McDonell M, Ginsberg RS, et al. Analysis of the effect of liposome encapsulation on the vesicant properties, acute and cardiac toxicities, and antitumor efficacy of doxorubicin. Cancer Chemother Pharmacol 1989; 23: 81–6.
  • 17
    Kanter PM, Bullard GA, Ginsberg RA, Pilkiewicz FG, Mayer LD, Cullis PR, et al. Comparison of the cardiotoxic effects of liposomal doxorubicin versus free doxorubicin in beagle dogs. In Vivo 1993; 7: 17–26.
  • 18
    Speyer JL, Green MD, Zeleniuch-Jacquotte A, Wernz JC, Rey M, Sanger J, et al. ICRF-187 permits longer treatment with doxorubicin in women with breast cancer. J Clin Oncol 1992; 10: 117–27.
  • 19
    Swain SM, Whaley FS, Gerber MC, Ewer MS, Bianchine JR, Gams RA. Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy. J Clin Oncol 1997; 15: 1333–40.
  • 20
    Tanabe K, Ikegami Y, Ishida R, Andoh T. Inhibition of topoisomerase II by antitumor agents bis(2,6-dioxopiperazine) derivatives. Cancer Res 1991; 51: 4903–8.
  • 21
    Hasinoff BB, Creighton AM, Kozlowska H, Thampatty P, Allan WP, Yalowich JC. Mitindomide is a catalytic inhibitor of DNA topoisomerase II that acts at the bisdioxopiperazine binding site. Mol Pharmacol 1997; 52: 839–45.
  • 22
    Coates A, Gebski V, Bishop JF, Jeal PN, Woods RL, Snyder R, et al. Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies. N Engl J Med 1987;317: 1490–5.
  • 23
    Muss HB, Case LD, Richards F, White DR, Cooper MR, Cruz JM, et al. Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. The Piedmont Oncology Association. N Engl J Med 1991;325: 1342–8.
  • 24
    Batist G, Ramakrishnan G, Rao CS, Chandrasekharan A, Gutheil J, Guthrie T, et al. Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. J Clin Oncol 2001; 19: 1444–54.
  • 25
    Chan S, Davidson N, Juozaityte E, Erdkamp F, Pluzanska A, Azarnia N, et al. Randomized trial of liposome-encapsulated doxorubicin and cyclophosphamide compared with epirubicin and cyclophosphamide in first-line therapy of metastatic breast cancer. (submitted).
  • 26
    Safra T, Muggia F, Jeffers S, Tsao-Wei DD, Groshen S, Lyass O, et al. Pegylated liposomal doxorubicin. Ann Oncol 2000; 11: 1029–33.
  • 27
    Nabholtz JM, Senn HJ, Bezwoda WR, Melnychuk D, Deschenes L, Douma J, et al. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. J Clin Oncol 1999; 17: 1413–24.
  • 28
    Bishop JF, Dewar J, Toner GC, Smith J, Tattersall MH, Olver IN, et al. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol 1999; 17: 2355–64.
  • 29
    Thor AD, Berry DA, Budman DR, Muss HB, Kute T, Henderson IC, et al. erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer. J Natl Cancer Inst 1998; 90: 1346–60.
  • 30
    Paik S, Bryant J, Park C, Fisher B, Tan-Chiu E, Hyams D, et al. erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst 1998; 90: 1361–70.
  • 31
    Theodoulou M, Campos S, Welles L, Batist G, Winer E, Hudis C. Preliminary cardiac safety and efficacy data from a phase I/II trial of TCL D-99 and trastuzumab in patients with locally advanced or metastatic breast cancer [abstract 180]. Proc Am Soc Clin Oncol 2001; 20: 46a.
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