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

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

Research output: Contribution to journalArticle

26 Scopus citations

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.

Original languageEnglish
Pages (from-to)453-458
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume61
Issue number3
DOIs
StatePublished - Mar 1 2008

Keywords

  • Colorectal cancer
  • MAC-321
  • Milataxel
  • Phase II
  • Taxanes

Fingerprint Dive into the research topics of 'A phase II study of milataxel: A novel taxane analogue in previously treated patients with advanced colorectal cancer'. Together they form a unique fingerprint.

  • Cite this

    Ramanathan, R. K., Picus, J., Raftopoulos, H., Bernard, S., Lockhart, A. C., Frenette, G., Macdonald, J., Melin, S., Berg, D., Brescia, F., Hochster, H., & Cohn, A. (2008). A phase II study of milataxel: A novel taxane analogue in previously treated patients with advanced colorectal cancer. Cancer Chemotherapy and Pharmacology, 61(3), 453-458. https://doi.org/10.1007/s00280-007-0489-5