Recurrent Epithelial Ovarian Carcinoma: A Randomized Phase III Study of Pegylated Liposomal Doxorubicin Versus Topotecan

Gordon, Alan N.; Fleagle, John; Guthrie, David; Parkin, David E.; Gore, Martin; Lacave, Ángel J.

doi:10.1200/jco.2001.19.14.3312

Cited by 1,094 publications

(802 citation statements)

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“…Mucositis was also rare and mild. No infusionrelated reactions, which are sometimes seen in cases of liposomal drug administration (Uziely et al, 1995;Muggia et al, 1996;Stewart et al, 1998;Gordon et al, 2001), occurred in this trial. Ultimately, this phase I study showed that the recommended dosage of NK911 (50 mg m À2 ) using a 3-week schedule was similar to the recommended dosage of free DXR (40 -60 mg m À2 ).…”

Section: Discussionmentioning

confidence: 65%

“…Doxil is comprised of doxorubicin (DXR) encapsulated in STEALTHt liposomes, which are composed of a phospholipid bilayer with surface-bound methoxypolyethyleneglycol. Doxil recently received the US Food and Drug Administration's (FDA) approval for use in the treatment of Kaposi sarcoma or ovarian cancer after the clinical benefits of this drug were clearly shown in recent clinical trials (Muggia et al, 1996;Stewart et al, 1998;Gordon et al, 2001).…”

mentioning

confidence: 99%

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Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin

Matsumura

Hamaguchi²,

Umemura³

et al. 2004

Br J Cancer

579

283

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NK911 is a novel supramolecular nanocarrier designed for the enhanced delivery of doxorubicin (DXR) and is one of the successful polymer micelle systems to exhibit an efficient accumulation in solid tumours in mice. The purpose of this study was to define the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of NK911 and to evaluate its pharmacokinetic profile in man. NK911 was given intravenously to patients with solid tumours every 3 weeks using an infusion pump at a rate of 10 mg DXR equivalent min À1 . The starting dose was 6 mg DXR equivalent m À2 , and the dose was escalated according to the accelerated titration method. A total of 23 patients participated in this study. Neutropenia was the predominant haematological toxicity, and grade 3 or 4 neutropenia was observed at doses of 50 and 67 mg m À2 . Common nonhaematological toxicities were mild alopecia, stomatitis, and anorexia. In the dose identification part of the study, DLTs were observed at a dose of 67 mg m À2 (grade 4 neutropenia lasting more than 5 days). Thus, this dosage level was determined to be the MTD. Infusion-related reactions were not observed in any cases. The C 5 min and area under the concentration curve parameters of NK911 exhibited dose-dependent characteristics. Among the 23 patients, a partial response was obtained in one patient with metastatic pancreatic cancer. NK911 was well tolerated and produced only moderate nausea and vomiting at myelosuppressive dosages. The recommended phase II dose was determined to be 50 mg m À2 every 3 weeks.

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Section: Discussionmentioning

confidence: 65%

mentioning

confidence: 99%

Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin

Matsumura

Hamaguchi²,

Umemura³

et al. 2004

Br J Cancer

579

283

View full text Add to dashboard Cite

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“…Substantial clinical activity with pegylated liposomal doxorubicin hydrochloride (PLD; Caelyx/Doxil s ) has been shown in patients refractory to paclitaxel and platinum-based chemotherapy (Gordon et al, 2001). Pegylated liposomal doxorubicin hydrochloride is a pegylated liposomal formulation of doxorubicin hydrochloride, which results in an altered kinetic profile, extending the half-life to 74 h. It is thought that the pegylated liposomal formulation may improve specificity of delivery to tumours, decreasing absorption by normal tissues, and may decrease many of the dose-limiting side effects of doxorubicin (Goram et al, 2001).…”

mentioning

confidence: 99%

“…The objective of this analysis is to determine the most cost-efficient therapy in the Spanish setting, since the clinical findings from a multicentre randomised trial showed that PLD was at least as efficacious as T (Gordon et al, 2001). An economic analysis has been performed in the form of a cost-minimisation analysis, in order to estimate and compare the costs associated with the two alternatives, PLD and T in Spain.…”

mentioning

confidence: 99%

Cost-minimisation analysis of pegylated liposomal doxorubicin hydrochloride versus topotecan in the treatment of patients with recurrent epithelial ovarian cancer in Spain

Ojeda

Sande²,

Casado

et al. 2003

Br J Cancer

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The study consisted of a cost-minimisation analysis since the findings from a multicentre randomised phase III trial showed that pegylated liposomal doxorubicin hydrochloride was at least as efficacious as topotecan. An economic model from the Spanish hospitals perspective was constructed to compare the costs derived from the treatment using both drugs in patients with recurrent epithelial ovarian cancer who failed a first-line platinum-containing regimen. The cost evaluation included direct medical costs: drug, drug administration and costs of managing adverse events. Estimation of resources used in managing adverse events was made retrospectively through an expert panel. Results obtained per patient were: cost of drug and administration, 8647.70 euros for pegylated liposomal doxorubicin hydrochloride and 8519.94 euros for topotecan, while cost of managing adverse events was 967.02 euros in the pegylated liposomal doxorubicin hydrochloride arm and 3304.75 euros for topotecan. The total cost per patient was therefore estimated to be 9614.72 euros for pegylated liposomal doxorubicin hydrochloride and 11 824.69 euros for topotecan, showing that pegylated liposomal doxorubicin hydrochloride produces a cost saving of 2209.97 euros per patient in comparison to topotecan. Sensitivity analyses verified the robustness of the results. These findings suggest that pegylated liposomal doxorubicin hydrochloride is an efficient therapy and can be used as a cost-saving option for treatment of patients with recurrent epithelial ovarian cancer who have failed a first-line platinum-containing regimen.

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“…[104,205] Furthermore, in other cancers like multiple myeloma and metastatic breast cancer, the therapeutic efficacy was equivalent to that of standard clinical therapies. [206,207] The main advantage of the Doxil in the therapy of solid tumors is the reduced cardiotoxicity, which is the adverse side effect caused by doxorubicin, as a result of the limited doxorubicin accumulation in heart. Nevertheless, Doxil have shown other side effects like hand-foot syndrome due to the extravasation into the skin facilitated by the prolonged circulation properties of Doxil.…”

Section: Cancer Nanomedicines From the Clinical Medicine Perspectivementioning

confidence: 99%

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Balasubramanian

Liu

Hirvonen

et al. 2017

Adv Healthcare Materials

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Explosive growth of nanomedicines continues to significantly impact the therapeutic strategies for effective cancer treatment. Despite the significant progress in the development of advanced nanomedicines, successful clinical translation remains challenging. As cancer nanomedicine is a multidisciplinary field, the fundamental problem is that the knowledge gaps stem from different vantage points in the understanding of cancer nanomedicines. The complexities and heterogenecity of both nanomedicines and cancer are further demanding the integration of highly diverse expertise to develop clinically translatable cancer nanomedicines. This progress report aims to discuss the current understanding of cancer nanomedicines between different research areas in terms of nanoparticle engineering, formulation, tumor patho-physiology and clinical medicine, as well as to identify the knowledge gaps lying at the interface between the different fields of research in nanomedicine. Here we also highlight for the necessity to harmonize the multidisciplinary effort in the research of nanomedicines in order to bridge the knowledge and to advance the full understanding in cancer nanomedicines. A paradigm shift is needed in the strategic development of disease specific nanomedicines in order to foster the successful translation into clinic of future cancer nanomedicines.

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Recurrent Epithelial Ovarian Carcinoma: A Randomized Phase III Study of Pegylated Liposomal Doxorubicin Versus Topotecan

Abstract: The comparable efficacy, favorable safety profile, and convenient dosing support the role of PLD as a valuable treatment option in this patient population.

Cited by 1,094 publications

References 30 publications

Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin

Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin

Cost-minimisation analysis of pegylated liposomal doxorubicin hydrochloride versus topotecan in the treatment of patients with recurrent epithelial ovarian cancer in Spain

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

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