Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Maximum Tolerated Dose and Pharmacokinetics of Paclitaxel Micellar in Patients with Recurrent Malignant Solid Tumours: A Dose-Escalation Study
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Show others and affiliations
2019 (English)In: Advances in Therapy, ISSN 0741-238X, E-ISSN 1865-8652, Vol. 36, no 5, p. 1150-1163Article in journal (Refereed) Published
Abstract [en]

Introduction: A water-soluble Cremophor EL-free formulation of paclitaxel, in which retinoic acid derivates solubilize paclitaxel by forming micelles (paclitaxel micellar), was studied for the first time in man to establish the maximum tolerated dose (MTD) and to characterize the pharmacokinetics (PK).

Methods: This was an open-label, one-arm, dose-escalating study in patients with advanced solid malignant tumours, for which no standard therapy was available or had failed. Paclitaxel micellar was given as 1-h intravenous infusion every 21 days for 3 cycles, mainly without premedication. Plasma samples were collected during 24 h at the first cycle and paclitaxel concentrations were assayed by high-performance liquid chromatography. PK was evaluated using a two-compartment model.

Results: Thirty-four patients received paclitaxel micellar at doses ranging between 90 and 275 mg/m2. MTD was established as 250 mg/m2. Fatigue and neuropathy were the most frequent dose-limiting toxicities. No hypersensitivity reactions were observed. PK of paclitaxel was evaluated in 25 data sets. Paclitaxel micellar had a rapid initial distribution phase, mean half-life 0.55 h, estimated to be completed 3 h after dosing and a mean terminal half-life of 8.8 h. Mean clearance was 13.4 L/h/m2 with fivefold interindividual variability. The residual areas after 10 h and 24 h were 15.7 ± 8.6% and 5.7 ± 3.9% of the area under the plasma concentration–time curve to infinite time (AUCinf), respectively.

Conclusion: No new side effects unknown for paclitaxel were observed. Maximum plasma concentration (Cmax) and AUCinf showed a tendency to increase linearly with dose within the 150–275 mg/m2dose range. The possibility to administer paclitaxel micellar without steroid premedication makes it an attractive candidate for further studies in combination with immunotherapy.

Trial Registration: EudraCT no: 2004-001821-54.

Place, publisher, year, edition, pages
Springer, 2019. Vol. 36, no 5, p. 1150-1163
Keywords [en]
Cancer, Dose-finding, First-in-man, Nano-sized micelles, Paclitaxel micellar, Paclitaxel, XR17, Pharmacokinetics
National Category
Cancer and Oncology Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:umu:diva-159064DOI: 10.1007/s12325-019-00909-6ISI: 000466110000014PubMedID: 30879251OAI: oai:DiVA.org:umu-159064DiVA, id: diva2:1316927
Available from: 2019-05-21 Created: 2019-05-21 Last updated: 2019-05-21Bibliographically approved

Open Access in DiVA

fulltext(1396 kB)51 downloads
File information
File name FULLTEXT01.pdfFile size 1396 kBChecksum SHA-512
6c3819533a8a8e9992e7608f9de1269aeeef173f0e66fae9e0a46b343953b6939173fb2f69a74ae2f298004ccafba6884417306934845838c618c74f19352340
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Henriksson, Roger
By organisation
Oncology
In the same journal
Advances in Therapy
Cancer and OncologyPharmacology and Toxicology

Search outside of DiVA

GoogleGoogle Scholar
Total: 51 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 134 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf