PMID- 19773753
OWN - NLM
STAT- MEDLINE
DCOM- 20091028
LR  - 20211020
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 101
IP  - 8
DP  - 2009 Oct 20
TI  - Weekly administration of sagopilone (ZK-EPO), a fully synthetic epothilone, in 
      patients with refractory solid tumours: results of a phase I trial.
PG  - 1241-7
LID - 10.1038/sj.bjc.6605327 [doi]
AB  - BACKGROUND: Epothilones are a novel class of microtubule-stabilising agents, and 
      sagopilone is a fully synthetic epothilone that has shown marked in vivo and in 
      vitro preclinical activity. METHODS: This phase I, open-label study investigated 
      the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of weekly 
      sagopilone. Twenty-three patients with malignancy resistant or refractory to 
      standard treatment were enrolled into this study evaluating sagopilone doses from 
      0.6 to 7.0 mg m(-2). RESULTS: The incidence of drug-related haematological 
      adverse events (AEs) was low, with two grade 3 events observed. Nonhaematological 
      AEs were generally mild and reversible; increased gamma-GT was the only grade 4 
      event and grade 3 events comprised peripheral neuropathy (n=2), diarrhoea (n=1) 
      and fatigue (n=1). Two grade 3 events were DLTs (diarrhoea and peripheral 
      neuropathy at 7.0 mg m(-2)). The MTD of weekly sagopilone was therefore 
      established as 5.3 mg m(-2). Stable disease was the best overall response (n=3). 
      Microtubule bundle formation in peripheral blood mononuclear cells increased 
      post-treatment, peaking after 1 h. Sagopilone disposition was similar across 
      treatment courses and showed rapidly decreasing serum concentrations after 
      infusion end and a long terminal disposition phase with no obvious accumulation 
      in the serum, probably reflecting a fast uptake into tissues followed by a slow 
      release. CONCLUSION: Weekly administration of sagopilone could represent an 
      alternative to the 3-weekly administration currently evaluated in phase II 
      trials.
FAU - Arnold, D
AU  - Arnold D
AD  - Department of Hematology and Oncology, Martin Luther University, Halle/Saale, 
      Germany. dirk.arnold@medizin.uni-halle.de
FAU - Voigt, W
AU  - Voigt W
FAU - Kiewe, P
AU  - Kiewe P
FAU - Behrmann, C
AU  - Behrmann C
FAU - Lindemann, S
AU  - Lindemann S
FAU - Reif, S
AU  - Reif S
FAU - Wiesinger, H
AU  - Wiesinger H
FAU - Giurescu, M
AU  - Giurescu M
FAU - Thiel, E
AU  - Thiel E
FAU - Schmoll, H-J
AU  - Schmoll HJ
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090922
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzothiazoles)
RN  - 0 (Epothilones)
RN  - KY72JU32FO (sagopilone)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/*therapeutic use
MH  - Benzothiazoles/*administration & dosage/adverse effects/pharmacokinetics
MH  - Drug Administration Schedule
MH  - Epothilones/*administration & dosage/adverse effects/pharmacokinetics
MH  - Female
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
PMC - PMC2768435
EDAT- 2009/09/24 06:00
MHDA- 2009/10/29 06:00
PMCR- 2010/10/20
CRDT- 2009/09/24 06:00
PHST- 2009/09/24 06:00 [entrez]
PHST- 2009/09/24 06:00 [pubmed]
PHST- 2009/10/29 06:00 [medline]
PHST- 2010/10/20 00:00 [pmc-release]
AID - 6605327 [pii]
AID - 10.1038/sj.bjc.6605327 [doi]
PST - ppublish
SO  - Br J Cancer. 2009 Oct 20;101(8):1241-7. doi: 10.1038/sj.bjc.6605327. Epub 2009 
      Sep 22.