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

Ramesk 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

24 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 (US)
Pages (from-to)453-458
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume61
Issue number3
DOIs
StatePublished - Mar 2008
Externally publishedYes

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Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

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