Patupilone in cancer treatment

Bystrický, Branislav; Chau, Ian

doi:10.1517/13543784.2011.542148

Cited by 26 publications

(15 citation statements)

References 46 publications

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“…Recently, several epothilones have been developed, which bind a similar site on tubulin but differ from the taxanes in specific binding characteristics, potency, and cross-resistance (28)(29)(30). A number of microtubule-stabilizing drug regimens are under investigation for refractory metastatic disease (31,32).…”

Section: Discussionmentioning

confidence: 99%

TPI-287, a New Taxane Family Member, Reduces the Brain Metastatic Colonization of Breast Cancer Cells

Fitzgerald

Emerson

Qian

et al. 2012

Molecular Cancer Therapeutics

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Brain metastases of breast and other cancers remain resistant to chemotherapeutic regimens that are effective systemically, in part due to the blood-brain barrier. We report that TPI-287, a new microtubule-stabilizing agent, displays in vitro cytotoxic activity similar to taxanes and epothilones. Unlike the taxanes, TPI-287 is permeable through the blood-brain barrier. Brain-to-plasma ratios of TPI-287 after a single injection typically exceeded one and were as high as 63.8 in the rat and 14.1 in the mouse. A brain-tropic derivative of the MDA-MB-231 triple-negative breast cancer cell line, 231-BR, was used to test whether TPI-287 may be efficacious at preventing or treating brain metastases. TPI-287 had growth inhibitory effects comparable with paclitaxel when 231-BR tumor cells were injected into the mammary fat pad. Brain metastatic colonization was determined by intracardiac injection of 231-BR cells, with treatment beginning on day 3 to 4 postinjection, culminating in a histologic count of brain metastases in brains necropsied days 25 to 28 postinjection. In this assay, paclitaxel, ixabepilone, and nab paclitaxel did not have significant inhibitory activity. TPI-287 was ineffective in the same assay using a 6 mg/kg every week schedule; however an 18 mg/kg dose delivered on days 3, 7, and 11 significantly reduced the outgrowth of brain metastases (55% reduction, P ¼ 0.028) and reduced proliferation in brain metastases (16% reduction, P ¼ 0.008). When TPI-287 treatment was delayed until days 18, 22, and 26 postinjection, efficacy was reduced (17% reduction, not significant). These data suggest that TPI-287 may have efficacy when administered early in the course of the disease.

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Section: Discussionmentioning

confidence: 99%

TPI-287, a New Taxane Family Member, Reduces the Brain Metastatic Colonization of Breast Cancer Cells

Fitzgerald

Emerson

Qian

et al. 2012

Molecular Cancer Therapeutics

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“…Although in a now completed phase III trial epothilone B does not achieve the effectivity of pegylated liposomal doxorubicin against refractory or relapsed ovarian cancer, it is still in clinical development for other cancers (e.g., central nervous system malignancies [6]), even in combination with radiotherapy [13,32].…”

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confidence: 99%

Radiosensitizing effect of epothilone B on human epithelial cancer cells

Baumgart¹,

Klautke²,

Kriesen³

et al. 2012

Strahlenther Onkol

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“…64 Clinical trials with Epo B (patupilone) have recently been reviewed. 65 Out of 350 epothilone analogs produced at Schering AG (now Bayer) by total synthesis up to 2006, the side chain-modified analog sagopilone (also known as ZK-EPO, 3; Figure 3.2) was chosen as a clinical candidate, since it combined high activity and efficacy with fast and efficient cellular uptake and was not recognized by drug efflux pumps. 66,67 In comparison with natural Epo B, sagopilone (3) features a benzothiazole-derived side chain and an allyl substituent at position 6; the former type of modification has independently been investigated by the group at Novartis/ETH Zürich (vide infra).…”

Section: Epothilone Bmentioning

confidence: 99%

Epothilones

Schiess

Altmann

2014

Macrocycles in Drug Discovery

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Epothilones A and B are naturally occurring microtubule stabilizers with nanomolar or even sub-nanomolar activity against human cancer cells in vitro and potent in vivo antitumor activity against multidrug-resistant tumors. Over the last decade, ten epothilonetype agents have entered clinical trials in humans; of these, the epothilone B lactam ixabepilone (BMS-247550; Ixempra®) was approved by the FDA for breast cancer treatment in 2007. Numerous synthetic and semisynthetic analogs of epothilones have been prepared and their in vitro and (in selected cases) in vivo biological activity has been determined, producing a wealth of SAR information on this compound family. This chapter will provide a brief summary of the in vitro and in vivo biological properties of epothilone B (Epo B). The major part of the discussion will then be organized around those epothilone analogs that have entered clinical development. For each analog the underlying synthetic chemistry and the most important preclinical features will be reviewed, together with the properties of some important related structures.

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Patupilone in cancer treatment

Abstract: Although patupilone has not demonstrated superiority over pegylated liposomal doxorubicin in a large Phase III trial in relapsed or refractory ovarian cancer, its evaluation is continuing in a range of other malignancies, especially in primary or secondary tumors of the CNS.

Cited by 26 publications

References 46 publications

TPI-287, a New Taxane Family Member, Reduces the Brain Metastatic Colonization of Breast Cancer Cells

TPI-287, a New Taxane Family Member, Reduces the Brain Metastatic Colonization of Breast Cancer Cells

Radiosensitizing effect of epothilone B on human epithelial cancer cells

Epothilones

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