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

Batist, Gerald; Ramakrishnan, G.; Rao, Chandra Sekhar; Chandrasekharan, Aruna; Gutheil, John; Guthrie, Troy H.; Shah, Pankaj; Khojasteh, Ali; Nair, Muralidharan; Hoelzer, Karen; Tkaczuk, Katherine H.; Park, Youn Choi; Lee, Lily W.

doi:10.1200/jco.2001.19.5.1444

Cited by 582 publications

(348 citation statements)

References 16 publications

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“…Myocet has been shown to improve the therapeutic index of doxorubicin by significantly reducing cardiotoxicity, allowing higher CD of doxorubicin to be administered (Batist et al, 2001). Further work would be required to definitively establish the CD for DaunoXome infusion bolus doses 5100 mg m 2 that should not be exceeded in order to prevent symptomatic cardiac toxicity.…”

Section: Discussionmentioning

confidence: 99%

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

et al. 2002

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The aims of this phase I study were to establish the maximum tolerated dose, safety profile and activity of liposomal daunorubicin, DaunoXome (NeXstar Pharmaceuticals), in the treatment of metastatic breast cancer. DaunoXome was administered intravenously over 2 h in 21 day cycles and doses were increased from 80 to 100, 120 and 150 mg m 2 . Sixteen patients were enrolled. A total of 70 cycles of DaunoXome were administered. The maximum tolerated dose was 120 mg m 2 , the dose-limiting toxicity being prolonged grade 4 neutropenia or neutropenic pyrexia necessitating dose reductions at 120 and 150 mg m 2 . Asymptomatic cardiotoxicity was observed in three patients: grade 1 in one treated with a cumulative dose of 800 mg m 2 and grade 2 in two, one who received a cumulative dose of 960 mg m 2 and the other a cumulative dose of 600 mg m 2 with a previous neoadjuvant doxorubicin chemotherapy of 300 mg m 2 . Tumour response was evaluable in 15 patients, of whom two had objective responses, six had stable disease and seven had progressive disease. In conclusion, DaunoXome is associated with mild, manageable toxicities and has anti-tumour activity in metastatic breast cancer. The findings support further phase II evaluation of DaunoXome alone and in combination with other standard nonanthracycline cytotoxic or novel targeted agents. Although the dose-limiting toxicity for DaunoXome was febrile neutropenia at 120 mg m 2 , we would recommend this dose for further evaluation, as the febrile neutropenia occurred after four or more cycles in three of the four episodes seen, was short lived and uncomplicated.

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Section: Discussionmentioning

confidence: 99%

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

et al. 2002

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“…The majority of clinical trials have been conducted in MBC; however, liposomal doxorubicin is also being studied in other tumor types, including non-Hodgkin's and AIDS-related lymphomas and Kaposi's sarcoma [20,21]. Several studies have been published that discuss the cardiac safety profile of liposomal doxorubicin in women with MBC [22][23][24]. Similar to what was observed with liposomal daunorubicin, higher doses of liposomal doxorubicin were associated with a greater risk for cardiotoxicity [24].…”

Section: Liposomal Doxorubicin (D-99)mentioning

confidence: 99%

Cardiac Safety of Liposomal Anthracyclines

Safra

2003

The Oncologist

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Anthracyclines have demonstrated antitumor activity in a variety of cancers; however, irreversible cardiac damage is a major dose-limiting toxicity, restricting lifetime cumulative dose. The most successful strategy to improve the cardiac safety of anthracyclines to date involves liposomal encapsulation, which alters the tissue distribution and pharmacokinetics of these agents. The cardiac safeties of liposomal daunorubicin, liposomal doxorubicin (D-99), and pegylated liposomal doxorubicin have been studied in several clinical trials. The lack of published data comparing liposomal daunorubicin with conventional daunorubicin makes it difficult to draw meaningful conclusions regarding the relative cardiac safeties of these formulations. Studies indicate that the risk of anthracycline-induced cardiotoxicity is considerably lower with liposomal doxorubicin formulations than with conventional doxorubicin. Pegylated liposomal doxorubicin has been studied most extensively and has demonstrated the most significant reductions in risk for cardiotoxicity. Compared with conventional doxorubicin, pegylated liposomal doxorubicin has shown similar efficacy with a significantly lower incidence of cardiotoxicity and significantly fewer cardiac events. Although the long-term cardiac safety of these agents is unknown, data suggest that liposomal anthracyclines, particularly pegylated liposomal doxorubicin, may offer a significant clinical benefit for patients with higher risks for anthracycline-induced cardiotoxicity. The Oncologist 2003;8(suppl 2):17-24 The Oncologist 2003;8(suppl 2):17-24 www.TheOncologist.com

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“…[22] udowodnili, że szczególną korzyść z leczenia doksorubicyną liposomalną uzyskują chore z przynajmniej jednym czynnikiem ryzyka wystąpienia niewydolności serca. Przy porównywalnej skuteczności przeciwnowotworowej łączny czas przeżycia był nieistotnie dłuższy (23 miesiące vs. 15 miesięcy) u chorych otrzymujących doksorubicynę liposomalną, a ryzyko sercowo-naczyniowe wynikające z działań niepożądanych było wielokrotnie mniejsze.…”

Section: Leczenie Doksorubicyną Wobec Codziennych Problemów Klinicznychunclassified

“…W badaniu III fazy porównującym schemat AC (doksorubicyna konwencjonalna) z MC (doksorubicyna liposomalna) u chorych na przerzutowego raka piersi wykazano podobną aktywność przeciwnowotworową obu schematów, przy wyraźnej różnicy w potencjale kardiotoksycznym (istotne klinicznie zdarzenia sercowe wynikające z kardiotoksyczności występowały przy istotnie niższych dawkach życiowych doksorubicyny konwencjonalnej w porównaniu z liposomalną) [22].…”

Section: Scenariusz Klinicznyunclassified

Liposomal doxorubicin in patients with breast cancer and concomitant cardiovascular diseases — interdisciplinary expert opinion

Szmit¹,

Filipiak‬²,

Litwiniuk³

et al. 2016

Kardiol Pol

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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

Abstract: Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.

Cited by 582 publications

References 16 publications

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

Cardiac Safety of Liposomal Anthracyclines

Liposomal doxorubicin in patients with breast cancer and concomitant cardiovascular diseases — interdisciplinary expert opinion

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