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01.03.2008 | Original Article

A phase II study of milataxel: a novel taxane analogue in previously treated patients with advanced colorectal cancer

verfasst von: Ramesh K. Ramanathan, Joel Picus, Haralambos Raftopoulos, Stephen Bernard, A. Craig Lockhart, Gary Frenette, John Macdonald, Susan Melin, Daniel Berg, Frank Brescia, Howard Hochster, Allen Cohn

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2008

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Abstract

Background

Milataxel is a novel taxane analog, with evidence of enhanced preclinical activity compared to paclitaxel and docetaxel, especially in cell lines that over express P-glycoprotein. Based on preclinical data that milataxel may be active in colorectal cancer (CRC), a phase II study was performed in patients with advanced previously treated CRC.

Patients and results

Forty-four eligible patients were entered. Milataxel was administered intravenously every 3 weeks at the dose of 35 mg/m². No objective responses were noted, stable disease was seen in three patients. The median time to progression was 1.4 months (95% CI of 1.2–2.4 months). Three subjects developed neutropenic sepsis and two died. The most frequent grade 3/4 adverse events were neutropenia (57%), leukopenia (27%), dehydration (14%), neuropathy (16%), diarrhea (14%) and thrombocytopenia (14%). The pharmacokinetics of milataxel was assessed in five subjects. The mean milataxel elimination half-life was 64 h and the mean area under the plasma concentration-time curve was 1,708 ng·h/ml.

Conclusions

A syndrome of neutropenic sepsis and diarrhea can be life threatening and close surveillance is needed in patients treated with milataxel at the dose of 35 mg/m² every 3 weeks. Clinical activity was not demonstrated in patients with advanced previously treated CRC.

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Titel: A phase II study of milataxel: a novel taxane analogue in previously treated patients with advanced colorectal cancer
verfasst von: Ramesh K. Ramanathan
Joel Picus
Haralambos Raftopoulos
Stephen Bernard
A. Craig Lockhart
Gary Frenette
John Macdonald
Susan Melin
Daniel Berg
Frank Brescia
Howard Hochster
Allen Cohn
Publikationsdatum: 01.03.2008
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 3/2008
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-007-0489-5

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A phase II study of milataxel: a novel taxane analogue in previously treated patients with advanced colorectal cancer