Feasibility and Cardiac Safety of Pegylated Liposomal Doxorubicin plus Trastuzumab in Heavily Pretreated Patients with Recurrent HER2-Overexpressing Metastatic Breast Cancer

Andreopoulou, Eleni; Gaiotti, Darci; Kim, Eugene; Volm, M; Oratz, Ruth; Freedberg, Robin S.; Downey, Andrea; Vogel, Charles L.; Chia, Stephen; Fm, Muggia

doi:10.3816/cbc.2007.n.028

Cited by 29 publications

(18 citation statements)

References 28 publications

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“…These data are in accordance to the two trials published by Chia et al and Andreopoulou et al, [14,15] which also assessed the cardiac toxicity of this regimen as first line therapy in MBC and reported only mild cardiac toxicity (Fig. 3).…”

Section: Discussionsupporting

confidence: 91%

“…3). Chia et al [14] found in 10% of the treated patients an absolute decline in LVEF of C15% but no symptomatic CHF. These data underline the excellent cardiac tolerability of the treatment combination PLD and trastuzumab, especially since all of these patients received prior anthracycline containing adjuvant treatment.…”

Section: Discussionmentioning

confidence: 97%

“…In 2007, Andreopoulou et al [14] conducted a second prospective phase II trial recruiting twelve patients. Three patients experienced grade 2 left ventricular dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial

Stickeler¹,

Klar²,

Watermann³

et al. 2009

Breast Cancer Res Treat

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The combination therapy of doxorubicin and trastuzumab has been proven to be highly effective for metastatic breast cancer (MBC) patients with Her2/neu over-expressing tumors. However, this regimen is characterized by frequent cardiac toxicity, occurring in 27% of all treated patients and aggravating when the two substances are given concurrently. Pegylated liposomal doxorubicin (PLD) as a single agent reduces significantly cardiac toxicity and maintains efficacy compared to conventional doxorubicin. This prospective open labeled, multicenter phase II study assessed the potential cardiotoxicity and efficacy of PLD and trastuzumab as first and second line combination therapy in Her2/neu over-expressing MBC patients. Patients with Her2 over-expressing, measurable MBC with a baseline left ventricular ejection fraction (LVEF) C50% were treated with PLD 40 mg/m 2 every 4 weeks for 6 up to 9 cycles and weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg). Cardiotoxicity was defined as the appearance of clinical signs or symptoms of congestive heart failure in combination with a decrease in LVEF B44% or C10 units below the normal value of 50% in the obligatory, subsequently performed transthoracic echocardiography. Due to conflicting interests, the planned accrual goal of 30 patients was not reached. Finally 16 patients were enrolled. Ten patients presented with more than one metastatic site and six of them were in second-line therapy. The median LVEF in the study cohort was 66.1 ± 8.68% at baseline, 62.7 ± 5.11% after 6 cycles of therapy, 64.4 ± 7.61% at the first follow up and did not change significantly (61.0 ± 5.56% even at the 5th followup). Six out of 12 assessable patients (50.0%) demonstrated a clinical benefit and after a median follow-up of 15.4 months a median progression free survival of 9.67 and a median overall survival of 16.23 months. Non-cardiac side effects were mild with only 3 CTC grade 3 events of 247 treatment cycles (1.2%) and no grade 4 toxicities. The combination of PLD and trastuzumab in patients with Her2/neu over-expressing metastatic breast cancer is a safe, feasible and effective therapy. However, cardiac function should be monitored at close intervals. Due to the promising clinical response rates and mild toxicity profile in this prognostically unfavorable group, this combination therapy should be evaluated in larger studies.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 97%

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Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial

Stickeler¹,

Klar²,

Watermann³

et al. 2009

Breast Cancer Res Treat

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“…The data reported by Stickeler et al find support in other small trials in which either pegylated [19][20][21] or nonpegylated doxorubicin [22] was combined with trastuzumab. Of note, in a Phase I/II trial that built on the combination of doxorubicin, paclitaxel and trastuzumab of the NOAH study and substituted the naked anthracycline with the non-pegylated liposomal formulation TLC-D99 the Authors reported an outstanding objective response rate of 98.1% in 69 patients with HER2-positive metastatic breast cancer, and a median time to progression exceeding 22 months at the cost of very good cardiac tolerability [23].…”

mentioning

confidence: 74%

Never use anthracyclines with trastuzumab: it is time to reconsider the taboo

Gianni

2009

Breast Cancer Res Treat

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“…Doxorubicin is an antibiotic drug widely used in chemotherapy, 14 and currently being tested in clinical trials for the treatment of several cancers. [15][16][17][18][19][20][21] It functions by intercalating with DNA and thus inhibiting DNA replication. It is commonly used in the treatment of a wide range of cancers.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of CD4+ T-cell help reverses the doxorubicin-induced suppression of antigen-specific immune responses in vaccinated mice

et al. 2008

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Feasibility and Cardiac Safety of Pegylated Liposomal Doxorubicin plus Trastuzumab in Heavily Pretreated Patients with Recurrent HER2-Overexpressing Metastatic Breast Cancer

Cited by 29 publications

References 28 publications

Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial

Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial

Never use anthracyclines with trastuzumab: it is time to reconsider the taboo

Enhancement of CD4+ T-cell help reverses the doxorubicin-induced suppression of antigen-specific immune responses in vaccinated mice

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