Thursday, November 4, 2010

Clinical Studies - Block Copolymers

A common question about block copolymers is are they in any current drug delivery formulations. The answer to that is that these copolymers are not in any FDA approved USA material yet however they have shown promise in clinical studies. There are currently clinical studies underway for Genexol system which delivers paclitaxel using a block copolymer of PEG-PLA. Similar block copolymers can be purchased from www.polyvivo.com

"ABSTRACT
Purpose: The rationale for developing an alternative
paclitaxel formulation concerns Cremophor EL-related side
effects, and a novel paclitaxel delivery system might augment
its therapeutic efficacy. Genexol-PM is a polymeric
micelle formulated paclitaxel free of Cremophor EL. A
phase I study was performed to determine the maximum
tolerated dosage, dose-limiting toxicities, and the pharmacokinetic
profile of Genexol-PM in patients with advanced,
refractory malignancies.
Experimental Design: Twenty-one patients were entered
into the study. Genexol-PM was i.v. administered over 3 h
every 3 weeks without premedication. The Genexol-PM dose
was escalated from 135 mg/m2 to 390 mg/m2.
Results: All of the patients were evaluable for toxicity
and response. Acute hypersensitivity reactions were not observed.
Neuropathy and myalgia were the most common
toxicities. During cycle 1, grade 3 myalgia occurred in 1
patient at 230 and 300 mg/m2, respectively. At 390 mg/m2, 2
of 3 patients developed grade 4 neutropenia or grade 3
polyneuropathy. Therefore, the maximum tolerated dosage
was determined to be 390 mg/m2. There were 3 partial
responses (14%) among the 21 patients. Of the 3 responders,
2 were refractory to prior taxane therapy. The paclitaxel
area under the curve from time 0 to infinity and peak or
maximum paclitaxel concentration seemed to increase with
escalating dose, except at 230 mg/m2, which suggests that
Genexol-PM has linear pharmacokinetics.
Conclusion: The main dose-limiting toxicities were neuropathy,
myalgia, and neutropenia, and the recommended
dosage for a phase II study is 300 mg/m2. Genexol-PM is
believed to be superior to conventional paclitaxel in terms of
the obviation of premedication and the delivery of higher
paclitaxel doses without additional toxicity. "

T.-Y. Kim, D.-W. Kim, J.-Y. Chung, S.G. Shin, S.-C. Kim, D.S. Heo, N.K. Kim, Y.-J. Bang, Phase I and Pharmacokinetic Study of Genexol-PM, a Cremophor-Free, Polymeric Micelle-Formulated Paclitaxel, in Patients with Advanced Malignancies Clin Cancer Res (2004). (link to full-text http://clincancerres.aacrjournals.org/content/10/11/3708.full.pdf+html)
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