Literature DB >> 22139065

First clinical pharmacokinetic dose-escalation study of sagopilone, a novel, fully synthetic epothilone, in Japanese patients with refractory solid tumors.

Kazuhiro Araki1, Koichi Kitagawa, Hirofumi Mukai, Toru Mukohara, Keiji Kodama, Yuichi Ando, Masaru Narabayashi, Hironobu Minami, Kiyomi Mera, Yasutsuna Sasaki.   

Abstract

PURPOSE: Sagopilone has recently been identified and preferentially used for the treatment of taxane-resistant cancer. The purpose of this dose-escalation study was to investigate the safety, tolerability, and pharmacokinetics (PK) of sagopilone in refractory solid tumors.
METHODS: A total of 17 Japanese patients received sagopilone in this Phase I study. Sagopilone was given as a 30-min intravenous infusion once every 3 weeks (one course) with an initial dose of 12.4 mg/m(2) up to 22.0 mg/m(2) for a maximum of 6 courses.
RESULTS: The maximum tolerated dose (MTD) was determined to be 16.5 mg/m(2). The major dose-limiting toxicity (DLT) was peripheral sensory neuropathy. The PK data demonstrated that sagopilone did not accumulate after repeated administration. Two patients had stable disease (SD) over a period of 12 weeks.
CONCLUSIONS: Our study demonstrated clinically favorable safety, tolerability, and efficacy of sagopilone, which will help define the treatment of advanced tumors in more extensive clinical trials.

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Year:  2011        PMID: 22139065     DOI: 10.1007/s10637-011-9773-7

Source DB:  PubMed          Journal:  Invest New Drugs        ISSN: 0167-6997            Impact factor:   3.850


  15 in total

Review 1.  Microtubules as a target for anticancer drugs.

Authors:  Mary Ann Jordan; Leslie Wilson
Journal:  Nat Rev Cancer       Date:  2004-04       Impact factor: 60.716

2.  Comparative profiling of the novel epothilone, sagopilone, in xenografts derived from primary non-small cell lung cancer.

Authors:  Stefanie Hammer; Anette Sommer; Iduna Fichtner; Michael Becker; Jana Rolff; Johannes Merk; Ulrich Klar; Jens Hoffmann
Journal:  Clin Cancer Res       Date:  2010-02-23       Impact factor: 12.531

3.  Total synthesis and antitumor activity of ZK-EPO: the first fully synthetic epothilone in clinical development.

Authors:  Ulrich Klar; Bernd Buchmann; Wolfgang Schwede; Werner Skuballa; Jens Hoffmann; Rosemarie B Lichtner
Journal:  Angew Chem Int Ed Engl       Date:  2006-12-04       Impact factor: 15.336

Review 4.  Microtubules and resistance to tubulin-binding agents.

Authors:  Maria Kavallaris
Journal:  Nat Rev Cancer       Date:  2010-02-11       Impact factor: 60.716

5.  Epothilons A and B: antifungal and cytotoxic compounds from Sorangium cellulosum (Myxobacteria). Production, physico-chemical and biological properties.

Authors:  K Gerth; N Bedorf; G Höfle; H Irschik; H Reichenbach
Journal:  J Antibiot (Tokyo)       Date:  1996-06       Impact factor: 2.649

6.  Phase I study of the novel, fully synthetic epothilone sagopilone (ZK-EPO) in patients with solid tumors.

Authors:  P Schmid; P Kiewe; K Possinger; A Korfel; S Lindemann; M Giurescu; S Reif; H Wiesinger; E Thiel; D Kühnhardt
Journal:  Ann Oncol       Date:  2009-10-30       Impact factor: 32.976

7.  A phase II trial evaluating two schedules of sagopilone (ZK-EPO), a novel epothilone, in patients with platinum-resistant ovarian cancer.

Authors:  G Rustin; N Reed; G C Jayson; J A Ledermann; M Adams; T Perren; C Poole; M Lind; M Persic; S Essapen; M Gore; H Calvert; C Stredder; A Wagner; M Giurescu; S Kaye
Journal:  Ann Oncol       Date:  2011-03-03       Impact factor: 32.976

8.  Docetaxel and cisplatin in combination as first-line chemotherapy for advanced epithelial ovarian cancer. Scottish Gynaecological Cancer Trials Group.

Authors:  P A Vasey; J Paul; A Birt; E J Junor; N S Reed; R P Symonds; R Atkinson; J Graham; S M Crawford; R Coleman; H Thomas; J Davis; S P Eggleton; S B Kaye
Journal:  J Clin Oncol       Date:  1999-07       Impact factor: 44.544

9.  Phase II study evaluating the efficacy and safety of sagopilone (ZK-EPO) in patients with metastatic breast cancer that has progressed following chemotherapy.

Authors:  Phuong K Morrow; Stephen Divers; Louise Provencher; Shiuh-Wen Luoh; Teresa M Petrella; Marius Giurescu; Thomas Schmelter; Yao Wang; Gabriel N Hortobagyi; Linda T Vahdat
Journal:  Breast Cancer Res Treat       Date:  2010-08-10       Impact factor: 4.872

10.  Weekly administration of sagopilone (ZK-EPO), a fully synthetic epothilone, in patients with refractory solid tumours: results of a phase I trial.

Authors:  D Arnold; W Voigt; P Kiewe; C Behrmann; S Lindemann; S Reif; H Wiesinger; M Giurescu; E Thiel; H-J Schmoll
Journal:  Br J Cancer       Date:  2009-09-22       Impact factor: 7.640

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  1 in total

1.  The Application of REDOR NMR to Understand the Conformation of Epothilone B.

Authors:  Jae-Ho Lee; Moon-Su Kim; Hyo Won Lee; Ihl-Young C Lee; Hyun Kyoung Kim; Nam Doo Kim; SangGap Lee; Hwajeong Seo; Younkee Paik
Journal:  Int J Mol Sci       Date:  2017-07-09       Impact factor: 5.923

  1 in total

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