A phase II study of patupilone in patients with metastatic hormone refractory prostate cancer (HRPC) who have progressed after docetaxel

N., K.; Beardsley, Emma Kate; Venner, Peter; Eigl, Bernhard J.; Hotte, S. J.; Ko, Yunmi; Saad, Fred; Winquist, Eric

doi:10.1200/jco.2008.26.15_suppl.5166

Cited by 14 publications

(12 citation statements)

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“…In patients with prostate cancer that was castrate resistant and taxane refractory, patupilone, ixabepilone, and KOS-862 have all decreased prostate specifi c antigen levels (Beer et al 2007;Rosenberg et al 2007;Chi et al 2008). In patients with castrate refractory metastatic prostate cancer tumors, but not chemotherapy-resistant tumors, patupilone, ixabepilone, and sagopilone induced prostate-specifi c antigen declines (Hussain et al 2004(Hussain et al , 2005Graff et al 2008).Ixabepilone has been studied in different dosing regimens with the once every 21 days dosing schedule compared with days 1, 8, 15 dosing every 28 days.…”

Section: Phase II Datamentioning

confidence: 99%

Novel microtubule-targeting agents – the epothilones

Cheng

Bradley²,

Budman

2008

BTT

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Epothilones are a new class of antimicrotubule agents currently in clinical trials. Their chemical structures are distinct from taxanes and are more amenable to synthetic modifi cation. Six epothilones have been studied in preclinical and clinical trials: patupilone (epothilone B), ixabepilone (BMS247550), BMS 310705, sagopilone (ZK-EPO), KOS-862 (epothilone D), and KOS-1584. In vitro data have shown increased potency in taxane-sensitive and taxane-resistant cancer cell lines. This enhanced cytotoxic effect has been attributed to epothilone being a poor substrate for p-glycoprotein drug resistance protein and having high affi nity to the various β tubulin isoforms. Phase I clinical data have shown different dose-limiting toxicities for each of the epothilones. These effects are drug specifi c, dose specifi c, and schedule of administration specifi c. While diarrhea and myelosuppression are the dose-limiting toxicities for patupilone and BMS 310705, respectively, neurologic toxicity, as seen with taxanes, is the dose-limiting toxicity of ixabepilone, sagopilone, and KOS-862. In an effort to decrease neurologic toxicity, investigators have modifi ed dosing schedules with limited success. Ixabepilone has the most mature clinical results with published phase II and III data, and regulatory approval for clinical use in the treatment of breast cancer. Ixabepilone has also been combined with other anticancer agents and has regulatory approval in combination with capecitabine for heavily treated breast cancer.

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Section: Phase II Datamentioning

confidence: 99%

Novel microtubule-targeting agents – the epothilones

Cheng

Bradley²,

Budman

2008

BTT

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“…In rodents, patupilone showed sustained anticancer effect in multidrug-resistant tumors, whereas paclitaxel has no significant effect [22]. Its antitumor activity has been demonstrated in several clinical trials with a number of tumor types, including ovarian, prostate, lung, and colon cancers [3,7,8,12,19,37,39].…”

Section: Introductionmentioning

confidence: 99%

Novel physiologically based pharmacokinetic modeling of patupilone for human pharmacokinetic predictions

Xia¹,

Heimbach²,

Lin³

et al. 2012

Cancer Chemother Pharmacol

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“…Patupilone was tolerated at the full dose in a phase I trial of taxane-refractory breast or prostate cancer when combined with estramustine (280 mg twice daily on days 1-3) and showed more activity, with one RECIST PR in 14 patients [59]. Patupilone was also evaluated as a single agent in a phase II trial in 77 men with CRPC who had progressed during or within 6 months of receiving docetaxel [43]. In the first stage of that two-stage trial, patients were treated with patupilone at a dose of 10 mg/m 2 i.v.…”

Section: Patupilonementioning

confidence: 99%

“…The dose-limiting toxicity (DLT) was fatigue with the weekly schedule, whereas neutropenia and mucositis were dose limiting with the 3-weekly dosing schedule; peripheral neuropathy was also a significant toxicity. Ixabepilone was evaluated in a series of early-phase studies in patients with CRPC (summarized in Table 1) [9,[43][44][45][46][47][48][49][50], with promising antitumor activity as monotherapy and in combination with mitoxantrone and prednisone in men who have progressed on docetaxel. Furthermore, antitumor activity with ixabepilone has been observed in the first-line and docetaxel-resistant settings.…”

Section: Clinical Experience With Epothilones In Crpc Ixabepilonementioning

confidence: 99%

The Epothilones: New Therapeutic Agents for Castration-Resistant Prostate Cancer

Dorff

Gross

2011

The Oncologist

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The management of castration-resistant prostate cancer (CRPC) presents a clinical challenge because of limitations in efficacy and durability with currently available therapeutics. The epothilones represent a novel class of anticancer therapy that stabilizes microtubules, causing cell death and tumor regression in preclinical models. The structure of the tubulin-binding site for epothilones is distinct from that of the taxanes. Moreover, preclinical studies suggest nonoverlapping mechanisms of resistance between epothilones and taxanes. In early-phase studies in patients with CRPC, treatment with ixabepilone, a semisynthetic analog of epothilone B, induced objective responses and prostatespecific antigen declines in men previously progressing on docetaxel-based regimens. Clinical activity has been observed in nonrandomized trials for patients with CRPC using ixabepilone in the first-and second-line settings as a single agent and in combination with estramustine. Patupilone and sagopilone were also shown to have promising efficacy in phase II clinical trials of patients with CRPC. All three epothilones appear to be well tolerated, with modest rates of neutropenia and peripheral neuropathy. The lack of crossresistance between epothilones and taxanes may allow sequencing of these agents. Evaluating epothilones in phase III comparative trials would provide much-needed insight into their potential place in the management of patients with CRPC. The Oncologist 2011;16:1349 -1358

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A phase II study of patupilone in patients with metastatic hormone refractory prostate cancer (HRPC) who have progressed after docetaxel

Cited by 14 publications

References 0 publications

Novel microtubule-targeting agents – the epothilones

Novel microtubule-targeting agents – the epothilones

Novel physiologically based pharmacokinetic modeling of patupilone for human pharmacokinetic predictions

The Epothilones: New Therapeutic Agents for Castration-Resistant Prostate Cancer

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A phase II study of patupilone in patients with metastatic hormone refractory prostate cancer (HRPC) who have progressed after docetaxel

Cited by 14 publications

References 0 publications

Novel microtubule-targeting agents &ndash; the epothilones

Novel microtubule-targeting agents &ndash; the epothilones

Novel physiologically based pharmacokinetic modeling of patupilone for human pharmacokinetic predictions

The Epothilones: New Therapeutic Agents for Castration-Resistant Prostate Cancer

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Product

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Novel microtubule-targeting agents – the epothilones

Novel microtubule-targeting agents – the epothilones