A phase I study of the safety and pharmacokinetics of trabectedin in combination with pegylated liposomal doxorubicin in patients with advanced malignancies

Mehren, Margaret von; Schilder, Russell J.; Cheng, Jonathan D.; Temmer, E.; Cardoso, Teresa; Renshaw, Frank Gary; Bayever, Eliel; Zannikos, Peter; Zhang, Yuan; Cohen, Roger B.

doi:10.1093/annonc/mdn363

Cited by 49 publications

(35 citation statements)

References 29 publications

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“…PLD have been extensively employed in some non-hematological neoplasm as breast cancer, with similar results in CR rate and OS to conventional doxorubicin [11,15] . But, most of these studies did not have a longer follow-up and only analyzed the presence of acute cardiac toxicity around the treatment and for < 2 years of follow-up.…”

Section: Discussionmentioning

confidence: 99%

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Aggressive chemotherapy in frail patients with diffuse large B-cell lymphoma: The role of pegylated liposomal doxorubicin

Neri¹,

Avilés²,

Schmitt³

et al. 2012

J Hemat Malig

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Background: Older patients with cardiac problems and diagnosis of diffuse large B-cell lymphoma generally are treated with reduced-dose chemotherapy and anthracyclines, the best drug in this malignancy, generally is omitted. Thus, survival is very poor in this setting of patients (< 20% at 3 years). Pegylated liposomal doxorubicin (PLD) has been showed clinical activity in younger patients and without excessive cardiac toxicity.

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Section: Discussionmentioning

confidence: 99%

“…The introduction of liposomal and pegylated liposomal anthracyclines open a new options in treatment of this setting of patients because these drugs showed similar antitumoral activity and reduced cardiac toxicity [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

Aggressive chemotherapy in frail patients with diffuse large B-cell lymphoma: The role of pegylated liposomal doxorubicin

Neri¹,

Avilés²,

Schmitt³

et al. 2012

J Hemat Malig

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“…Trabectedin is demonstrated to be active in breast, ovarian, nonsmall cell lung cancers, melanoma and sarcoma and several reports showed that it could be safely combined with other agents such as gemcitabine and PLD [72][73][74]. Monk reported a phase III study on recurrent, partially platinum-sensitive OCs treated with trabectedin plus PLD.…”

Section: Beyond Platinum-based Chemotherapy: Towards a Personalized Tmentioning

confidence: 99%

Ovarian Cancer: BRCA Genetics Reveals Targets for New Therapies

Artioli¹,

Borgato²,

Ausoni³

et al. 2014

J Genet Syndr Gene Ther

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Ovarian cancer is the most lethal gynecological malignancy and the fifth cause of cancer mortality in women in the Western Countries. Advanced genomic analysis showed that most hereditary and a large proportion of sporadic ovarian cancers are associated with genetic and epigenetic aberrations either in BRCA1 and/or BRCA2 genes or in other genes involved in DNA repair and genomic stability. BRCA dysfunction identifies a major subset of ovarian cancers with peculiar epidemiological and clinical features, such as higher incidence in younger females, high-grade serous phenotype, better chemosensitivity and outcome. Being particularly sensitive to DNA-damaging agents, such as platinum compounds, these tumors are suitable for new therapeutic options that represent future challenges for oncologists. In this article we review the known molecular dysfunction in hereditary ovarian cancers and BRCAness and discuss the implications of new advances for more personalized treatments.

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“…Several Phase I trials of trabectedin-based combinations have been reported, and showed that trabectedin could be safely combined with doxorubicin, 27,28 PLD, 29 gemcitabine, 30 taxanes, 31,32 and capecitabine. 33 A recently published article has reported on a Phase I trial investigating the combination of trabectedin and cisplatin.…”

Section: Trabectedin-based Combinationsmentioning

confidence: 99%

“…29 Thirty-six patients with normal liver function, prior doxorubicin exposure , 250 mg/m², and normal cardiac function were enrolled. A broad range of advanced malignancies was represented, the most common being sarcoma (n = 16), ovarian cancer (n = 4), and pancreatic cancer (n = 2).…”

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confidence: 99%

New developments in treatment of ovarian carcinoma: focus on trabectedin

Cassier¹

2010

CMAR

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Abstract:Trabectedin is a new marine-derived compound that binds the DNA minor groove and interacts with proteins of the DNA repair machinery. Trabectedin has shown promising single-agent activity in pretreated patients with soft tissue sarcoma, and ovarian and breast cancer, and combination with various other chemotherapeutic drugs seems feasible. Toxicities are mainly hematologic and hepatic, with Grade 3-4 neutropenia and thrombocytopenia observed in approximately 50% and 20% of patients, respectively, and Grade 3-4 elevation of liver enzymes observed in 35%-50% of patients treated with trabectedin. The recently reported results of a large Phase III trial comparing pegylated liposomal doxorubicin (PLD) alone with a combination of PLD and trabectedin in patients with recurrent ovarian cancer showed improved progression-free survival with the combination of trabectedin and PLD, albeit at the price of increased toxicity. Current research focuses on the identification of predictive factors for patients treated with trabectedin, as well as the development of other combinations.

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A phase I study of the safety and pharmacokinetics of trabectedin in combination with pegylated liposomal doxorubicin in patients with advanced malignancies

Abstract: Trabectedin combined with PLD is generally well tolerated at therapeutic doses of both drugs in pretreated patients with diverse tumor types and appears to provide clinical benefit. These results support the need for additional studies of this combination in appropriate cancer types.

Cited by 49 publications

References 29 publications

Aggressive chemotherapy in frail patients with diffuse large B-cell lymphoma: The role of pegylated liposomal doxorubicin

Aggressive chemotherapy in frail patients with diffuse large B-cell lymphoma: The role of pegylated liposomal doxorubicin

Ovarian Cancer: BRCA Genetics Reveals Targets for New Therapies

New developments in treatment of ovarian carcinoma: focus on trabectedin

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