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

  • Cancer Chemother Pharmacol. 2008 Mar;61(3):453-8. doi: 10.1007/s00280-007-0489-5.
Ramesh K Ramanathan  1 ,  Joel Picus ,  Haralambos Raftopoulos ,  Stephen Bernard ,  A Craig Lockhart ,  Gary Frenette ,  John Macdonald ,  Susan Melin ,  Daniel Berg ,  Frank Brescia ,  Howard Hochster ,  Allen Cohn
Affiliations
  • 1. Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. [email protected]
PMID: 17516069 DOI: 10.1007/s00280-007-0489-5
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/m(2). 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/m(2) every 3 weeks. Clinical activity was not demonstrated in patients with advanced previously treated CRC.

Products