Skip to main content
Top
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Single-agent pegylated liposomal doxorubicin (PLD) in the treatment of metastatic breast cancer: results of an Austrian observational trial

Authors: Michael Fiegl, Brigitte Mlineritsch, Michael Hubalek, Rupert Bartsch, Ursula Pluschnig, Günther G Steger

Published in: BMC Cancer | Issue 1/2011

Login to get access

Abstract

Background

In advanced breast cancer, multiple sequential lines of treatments are frequently applied. Pegylated liposomal doxorubicin (PLD) has a favourable toxicity profile and can be used in first or higher lines of therapy. PLD has demonstrated response activity even after prior anthracycline exposure.

Methods

129 consecutive patients with advanced breast cancer, of whom the majority had been massively pretreated, received PLD as monotherapy within licensed approval, for which efficacy and toxicities were documented.

Results

In a routine therapy setting, PLD was administered in a slightly reduced dose (median, 40 mg/m2 per cycle). Response rate (complete and partial remission) was 26%, and stable disease was observed in 19% of patients. Progression-free (PFS) and overall survival (OS) were 5.8 months and 14.2 months, respectively. There was no difference in terms of response and PFS, no matter if patients had already received anthracycline treatment. Interestingly, PFS proved similar regardless whether PLD was administered as palliative therapy in first, second or third line. Furthermore, PFS and OS were similar in patients with response or stable disease, underscoring the view that disease stabilization is associated with a profound clinical benefit. The most common side effects reported were palmar-plantar erythrodysesthesia (17%), exanthema (14%) and mucositis (12%).

Conclusions

Efficacy and toxicity data in these "real life" patients permit the conclusion that PLD is a valuable option in the treatment of advanced breast cancer even in heavily pretreated patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference Beslija S, Bonneterre J, Burstein HJ, Cocquyt V, Gnant M, Heinemann V, Jassem J, Köstler WJ, Krainer M, Menard S, Petit T, Petruzelka L, Possinger K, Schmid P, Stadtmauer E, Stockler M, Van Belle S, Vogel C, Wilcken N, Wiltschke C, Zielinski CC, Zwierzina H, Central European Cooperative Oncology Group (CECOG): Third consensus on medical treatment of metastatic breast cancer. Ann Oncol. 2009, 20: 1771-85. 10.1093/annonc/mdp261.CrossRefPubMed Beslija S, Bonneterre J, Burstein HJ, Cocquyt V, Gnant M, Heinemann V, Jassem J, Köstler WJ, Krainer M, Menard S, Petit T, Petruzelka L, Possinger K, Schmid P, Stadtmauer E, Stockler M, Van Belle S, Vogel C, Wilcken N, Wiltschke C, Zielinski CC, Zwierzina H, Central European Cooperative Oncology Group (CECOG): Third consensus on medical treatment of metastatic breast cancer. Ann Oncol. 2009, 20: 1771-85. 10.1093/annonc/mdp261.CrossRefPubMed
2.
go back to reference Prassl K, Sahanic A, Reicher B, Denz H, Freund M, Fiegl M: Striking response with bevacizumab and chemotherapy in a woman with heavily pretreated breast cancer: a case presentation. Memo. 2008, 1: 149-51.CrossRef Prassl K, Sahanic A, Reicher B, Denz H, Freund M, Fiegl M: Striking response with bevacizumab and chemotherapy in a woman with heavily pretreated breast cancer: a case presentation. Memo. 2008, 1: 149-51.CrossRef
3.
go back to reference Northfelt DW, Martin FJ, Working P, Volberding PA, Russell J, Newman M, Amantea MA, Kaplan LD: Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi's sarcoma. J Clin Pharmacol. 1996, 36: 55-63.CrossRefPubMed Northfelt DW, Martin FJ, Working P, Volberding PA, Russell J, Newman M, Amantea MA, Kaplan LD: Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi's sarcoma. J Clin Pharmacol. 1996, 36: 55-63.CrossRefPubMed
4.
go back to reference Mlineritsch B, Mayer P, Rass C, Reiter E, Russ G, Vesenmayer G, Oberaigner W, Hausmaninger H: Phase II study of single-agent pegylated liposomal doxorubicin HCl (PLD) in metastatic breast cancer after first-line treatment failure. Onkologie. 2004, 27: 441-46. 10.1159/000080363.PubMed Mlineritsch B, Mayer P, Rass C, Reiter E, Russ G, Vesenmayer G, Oberaigner W, Hausmaninger H: Phase II study of single-agent pegylated liposomal doxorubicin HCl (PLD) in metastatic breast cancer after first-line treatment failure. Onkologie. 2004, 27: 441-46. 10.1159/000080363.PubMed
5.
go back to reference Huober J, Fett W, Nusch A, Neise M, Schmidt M, Wischnik A, Gerhardt S, Goehler T, Lück HJ, Rost A: A multicentric observational trial of pegylated liposomal doxorubicin for metastatic breast cancer. BMC Cancer. 2010, 10: 2-10.1186/1471-2407-10-2.CrossRefPubMedPubMedCentral Huober J, Fett W, Nusch A, Neise M, Schmidt M, Wischnik A, Gerhardt S, Goehler T, Lück HJ, Rost A: A multicentric observational trial of pegylated liposomal doxorubicin for metastatic breast cancer. BMC Cancer. 2010, 10: 2-10.1186/1471-2407-10-2.CrossRefPubMedPubMedCentral
6.
go back to reference Al-Batran SE, Bischoff J, von Minckwitz G, Atmaca A, Kleeberg U, Meuthen I, Morack G, Lerbs W, Hecker D, Sehouli J, Knuth A, Jager E: The clinical benefit of pegylated liposomal doxorubicin in patients with metastatic breast cancer previously treated with conventional anthracyclines: a multicentre phase II trial. Br J Cancer. 2006, 94: 1615-20.PubMedPubMedCentral Al-Batran SE, Bischoff J, von Minckwitz G, Atmaca A, Kleeberg U, Meuthen I, Morack G, Lerbs W, Hecker D, Sehouli J, Knuth A, Jager E: The clinical benefit of pegylated liposomal doxorubicin in patients with metastatic breast cancer previously treated with conventional anthracyclines: a multicentre phase II trial. Br J Cancer. 2006, 94: 1615-20.PubMedPubMedCentral
7.
go back to reference Ranson MR, 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, 15: 3185-91.PubMed Ranson MR, 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, 15: 3185-91.PubMed
8.
go back to reference Lyass O, Uziely B, Ben-Yosef R, Tzemach D, Heshing NI, Lotem M, Brufman G, Gabizon A: Correlation of toxicity with pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in metastatic breast carcinoma. Cancer. 2000, 89: 1037-47. 10.1002/1097-0142(20000901)89:5<1037::AID-CNCR13>3.0.CO;2-Z.CrossRefPubMed Lyass O, Uziely B, Ben-Yosef R, Tzemach D, Heshing NI, Lotem M, Brufman G, Gabizon A: Correlation of toxicity with pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in metastatic breast carcinoma. Cancer. 2000, 89: 1037-47. 10.1002/1097-0142(20000901)89:5<1037::AID-CNCR13>3.0.CO;2-Z.CrossRefPubMed
9.
go back to reference O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C: CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004, 15: 440-49. 10.1093/annonc/mdh097.CrossRefPubMed O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C: CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004, 15: 440-49. 10.1093/annonc/mdh097.CrossRefPubMed
10.
go back to reference Keller AM, Mennel RG, Georgoulias VA, Nabholtz JM, Erazo A, Lluch A, Vogel CL, Kaufmann M, von Minckwitz G, Henderson IC, Mellars L, Alland L, Tendler C: Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer. J Clin Oncol. 2004, 22: 3893-901. 10.1200/JCO.2004.08.157.CrossRefPubMed Keller AM, Mennel RG, Georgoulias VA, Nabholtz JM, Erazo A, Lluch A, Vogel CL, Kaufmann M, von Minckwitz G, Henderson IC, Mellars L, Alland L, Tendler C: Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer. J Clin Oncol. 2004, 22: 3893-901. 10.1200/JCO.2004.08.157.CrossRefPubMed
11.
go back to reference Coleman RE, Biganzoli L, Canney P, Dirix L, Mauriac L, Chollet P, Batter V, Ngalula-Kabanga E, Dittrich C, Piccart M: A randomised phase II study of two different schedules of pegylated liposomal doxorubicin in metastatic breast cancer (EORTC-10993). Eur J Cancer. 2006, 42: 882-87. 10.1016/j.ejca.2005.12.011.CrossRefPubMed Coleman RE, Biganzoli L, Canney P, Dirix L, Mauriac L, Chollet P, Batter V, Ngalula-Kabanga E, Dittrich C, Piccart M: A randomised phase II study of two different schedules of pegylated liposomal doxorubicin in metastatic breast cancer (EORTC-10993). Eur J Cancer. 2006, 42: 882-87. 10.1016/j.ejca.2005.12.011.CrossRefPubMed
12.
go back to reference Lorusso D, Di Stefano A, Carone V, Fagotti A, Pisconti S, Scambia G: Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia ('hand-foot' syndrome). Ann Oncol. 2007, 18: 1159-64. 10.1093/annonc/mdl477.CrossRefPubMed Lorusso D, Di Stefano A, Carone V, Fagotti A, Pisconti S, Scambia G: Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia ('hand-foot' syndrome). Ann Oncol. 2007, 18: 1159-64. 10.1093/annonc/mdl477.CrossRefPubMed
13.
go back to reference Vardy J, Dadasovich R, Beale P, Boyer M, Clarke SJ: Eligibility of patients with advanced non-small cell lung cancer for phase III chemotherapy trials. BMC Cancer. 2009, 9: 130-10.1186/1471-2407-9-130.CrossRefPubMedPubMedCentral Vardy J, Dadasovich R, Beale P, Boyer M, Clarke SJ: Eligibility of patients with advanced non-small cell lung cancer for phase III chemotherapy trials. BMC Cancer. 2009, 9: 130-10.1186/1471-2407-9-130.CrossRefPubMedPubMedCentral
14.
go back to reference Fiegl M, Falkner A, Hopfinger G, Brugger S, Zabernigg A, Bauer F, Haslbauer F, Demirtas D, Grossschmidt P, Tatzreiter G, Gastl G, Greil R, Austrian Collaborative Study Group on Alemtuzumab in Chronic Lymphocytic Leukemia: Routine clinical use of alemtuzumab in patients with heavily pretreated B-cell chronic lymphocytic leukemia: a nation-wide retrospective study in Austria. Cancer. 2006, 107: 2408-16. 10.1002/cncr.22263.CrossRefPubMed Fiegl M, Falkner A, Hopfinger G, Brugger S, Zabernigg A, Bauer F, Haslbauer F, Demirtas D, Grossschmidt P, Tatzreiter G, Gastl G, Greil R, Austrian Collaborative Study Group on Alemtuzumab in Chronic Lymphocytic Leukemia: Routine clinical use of alemtuzumab in patients with heavily pretreated B-cell chronic lymphocytic leukemia: a nation-wide retrospective study in Austria. Cancer. 2006, 107: 2408-16. 10.1002/cncr.22263.CrossRefPubMed
15.
go back to reference Bartsch R, Wenzel C, Altorjai G, Pluschnig U, Rudas M, Mader RM, Gnant M, Zielinski CC, Steger GG: Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer. J Clin Oncol. 2007, 25: 3853-8. 10.1200/JCO.2007.11.9776.CrossRefPubMed Bartsch R, Wenzel C, Altorjai G, Pluschnig U, Rudas M, Mader RM, Gnant M, Zielinski CC, Steger GG: Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer. J Clin Oncol. 2007, 25: 3853-8. 10.1200/JCO.2007.11.9776.CrossRefPubMed
16.
go back to reference Bartsch R, De Vries C, Pluschnig U, Dubsky P, Bago-Horvath Z, Gampenrieder SP, Rudas M, Mader RM, Rottenfusser A, Wiltschke C, Gnant M, Zielinski CC, Steger GG: Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer. BMC Cancer. 2009, 9: 367-10.1186/1471-2407-9-367.CrossRefPubMedPubMedCentral Bartsch R, De Vries C, Pluschnig U, Dubsky P, Bago-Horvath Z, Gampenrieder SP, Rudas M, Mader RM, Rottenfusser A, Wiltschke C, Gnant M, Zielinski CC, Steger GG: Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer. BMC Cancer. 2009, 9: 367-10.1186/1471-2407-9-367.CrossRefPubMedPubMedCentral
17.
go back to reference Bartsch R, Mlineritsch B, Gnant M, Niernberger T, Pluschnig U, Greil R, Wenzel C, Sevelda P, Thaler J, Rudas M, Pober M, Zielinski CC, Steger GG, Austrian Fulvestrant Registry: The Austrian fulvestrant registry: results from a prospective observation of fulvestrant in postmenopausal patients with metastatic breast cancer. Breast Cancer Res Treat. 2009, 115: 373-80. 10.1007/s10549-008-0132-0.CrossRefPubMed Bartsch R, Mlineritsch B, Gnant M, Niernberger T, Pluschnig U, Greil R, Wenzel C, Sevelda P, Thaler J, Rudas M, Pober M, Zielinski CC, Steger GG, Austrian Fulvestrant Registry: The Austrian fulvestrant registry: results from a prospective observation of fulvestrant in postmenopausal patients with metastatic breast cancer. Breast Cancer Res Treat. 2009, 115: 373-80. 10.1007/s10549-008-0132-0.CrossRefPubMed
18.
go back to reference Fiegl M, Hilbe W, Auberger J, Schmid T, Auberger T, Tzankov A, Sterlacci W, Denz H, Jamnig H, Greil R: Twelve-year retrospective analysis of lung cancer--The TYROL Study: Daily routine in 1,424 patients (1995-2006). J Clin Oncol. 2008, 26 (15S): 19063- Fiegl M, Hilbe W, Auberger J, Schmid T, Auberger T, Tzankov A, Sterlacci W, Denz H, Jamnig H, Greil R: Twelve-year retrospective analysis of lung cancer--The TYROL Study: Daily routine in 1,424 patients (1995-2006). J Clin Oncol. 2008, 26 (15S): 19063-
19.
go back to reference Perez AT, Domenech GH, Frankel C, Vogel CL: Pegylated liposomal doxorubicin (Doxil) for metastatic breast cancer: the Cancer Research Network, Inc., experience. Cancer Invest. 2002, 20 (Suppl 2): 2-29. Perez AT, Domenech GH, Frankel C, Vogel CL: Pegylated liposomal doxorubicin (Doxil) for metastatic breast cancer: the Cancer Research Network, Inc., experience. Cancer Invest. 2002, 20 (Suppl 2): 2-29.
20.
go back to reference Al-Batran SE, Meerpohl HG, von Minckwitz G, Atmaca A, Kleeberg U, Harbeck N, Lerbs W, Hecker D, Sehouli J, Knuth A, Jager E: Reduced incidence of severe palmar-plantar erythrodysesthesia and mucositis in a prospective multicenter phase II trial with pegylated liposomal doxorubicin at 40 mg/m2 every 4 weeks in previously treated patients with metastatic breast cancer. Oncology. 2006, 70: 141-46. 10.1159/000093005.CrossRefPubMed Al-Batran SE, Meerpohl HG, von Minckwitz G, Atmaca A, Kleeberg U, Harbeck N, Lerbs W, Hecker D, Sehouli J, Knuth A, Jager E: Reduced incidence of severe palmar-plantar erythrodysesthesia and mucositis in a prospective multicenter phase II trial with pegylated liposomal doxorubicin at 40 mg/m2 every 4 weeks in previously treated patients with metastatic breast cancer. Oncology. 2006, 70: 141-46. 10.1159/000093005.CrossRefPubMed
21.
go back to reference Sun WL, Hutarew G, Gradl J, Gratzl M, Heumader E, Denz H, Fiegl M: Bevacizumab-based combination therapy in a patient with pseudomyxoma peritonei. Memo. 2009, 2: 113-15. 10.1007/s12254-009-0113-y.CrossRef Sun WL, Hutarew G, Gradl J, Gratzl M, Heumader E, Denz H, Fiegl M: Bevacizumab-based combination therapy in a patient with pseudomyxoma peritonei. Memo. 2009, 2: 113-15. 10.1007/s12254-009-0113-y.CrossRef
22.
go back to reference Al-Batran SE, Güntner M, Pauligk C, Scholz M, Chen R, Beiss B, Stopatschinskaja S, Lerbs W, Harbeck N, Jäger E: Anthracycline rechallenge using pegylated liposomal doxorubicin in patients with metastatic breast cancer: a pooled analysis using individual data from four prospective trials. Br J Cancer. 2010, 103: 1518-23. 10.1038/sj.bjc.6605961.CrossRefPubMedPubMedCentral Al-Batran SE, Güntner M, Pauligk C, Scholz M, Chen R, Beiss B, Stopatschinskaja S, Lerbs W, Harbeck N, Jäger E: Anthracycline rechallenge using pegylated liposomal doxorubicin in patients with metastatic breast cancer: a pooled analysis using individual data from four prospective trials. Br J Cancer. 2010, 103: 1518-23. 10.1038/sj.bjc.6605961.CrossRefPubMedPubMedCentral
23.
go back to reference Alba E, Ruiz-Borrego M, Margelí M, Rodríguez-Lescure A, Sánchez-Rovira P, Ruiz A, Mel-Lorenzo JR, Ramos-Vázquez M, Ribelles N, Calvo E, Casado A, Márquez A, Vicente D, García-Sáenz JA, Martín M: Maintenance treatment with pegylated liposomal doxorubicin versus observation following induction chemotherapy for metastatic breast cancer: GEICAM 2001-01 study. Breast Cancer Res Treat. 2010, 122: 169-76. 10.1007/s10549-010-0860-9.CrossRefPubMed Alba E, Ruiz-Borrego M, Margelí M, Rodríguez-Lescure A, Sánchez-Rovira P, Ruiz A, Mel-Lorenzo JR, Ramos-Vázquez M, Ribelles N, Calvo E, Casado A, Márquez A, Vicente D, García-Sáenz JA, Martín M: Maintenance treatment with pegylated liposomal doxorubicin versus observation following induction chemotherapy for metastatic breast cancer: GEICAM 2001-01 study. Breast Cancer Res Treat. 2010, 122: 169-76. 10.1007/s10549-010-0860-9.CrossRefPubMed
24.
go back to reference Murphy CG, Khasraw M, Seidman AD: Holding back the sea: the role for maintenance chemotherapy in metastatic breast cancer. Breast Cancer Res Treat. 2010, 122: 177-9. 10.1007/s10549-010-0925-9.CrossRefPubMed Murphy CG, Khasraw M, Seidman AD: Holding back the sea: the role for maintenance chemotherapy in metastatic breast cancer. Breast Cancer Res Treat. 2010, 122: 177-9. 10.1007/s10549-010-0925-9.CrossRefPubMed
25.
go back to reference Von Moos R, Thuerlimann BJ, Aapro M, Rayson D, Harrold K, Sehouli J, Scotte F, Lorusso D, Dummer R, Lacouture ME, Lademann J, Hauschild A: Pegylated liposomal doxorubicin-associated hand-foot syndrome: recommendations of an international panel of experts. Eur J Cancer. 2008, 44: 781-90. 10.1016/j.ejca.2008.01.028.CrossRefPubMed Von Moos R, Thuerlimann BJ, Aapro M, Rayson D, Harrold K, Sehouli J, Scotte F, Lorusso D, Dummer R, Lacouture ME, Lademann J, Hauschild A: Pegylated liposomal doxorubicin-associated hand-foot syndrome: recommendations of an international panel of experts. Eur J Cancer. 2008, 44: 781-90. 10.1016/j.ejca.2008.01.028.CrossRefPubMed
26.
go back to reference Broeyer FJ, Osanto S, Ritsema van Eck HJ, van Steijn AQ, Ballieux BE, Schoemaker RC, Cohen AF, Burggraaf J: Evaluation of biomarkers for cardiotoxicity of anthracyclin-based chemotherapy. J Cancer Res Clin Oncol. 2008, 134: 961-68. 10.1007/s00432-008-0372-8.CrossRefPubMedPubMedCentral Broeyer FJ, Osanto S, Ritsema van Eck HJ, van Steijn AQ, Ballieux BE, Schoemaker RC, Cohen AF, Burggraaf J: Evaluation of biomarkers for cardiotoxicity of anthracyclin-based chemotherapy. J Cancer Res Clin Oncol. 2008, 134: 961-68. 10.1007/s00432-008-0372-8.CrossRefPubMedPubMedCentral
Metadata
Title
Single-agent pegylated liposomal doxorubicin (PLD) in the treatment of metastatic breast cancer: results of an Austrian observational trial
Authors
Michael Fiegl
Brigitte Mlineritsch
Michael Hubalek
Rupert Bartsch
Ursula Pluschnig
Günther G Steger
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-373

Other articles of this Issue 1/2011

BMC Cancer 1/2011 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine