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

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.

• Authors: 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
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 61 Issue 3 Pg. 453-8 (Mar 2008) ISSN: 0344-5704 [Print] Germany
• PMID: 17516069 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• MAC321
• Paclitaxel

Topics

• Adult
• Aged
• Antineoplastic Agents, Phytogenic (adverse effects, pharmacokinetics, therapeutic use)
• Area Under Curve
• Blood Cell Count
• Colorectal Neoplasms (drug therapy)
• Dose-Response Relationship, Drug
• Female
• Half-Life
• Humans
• Male
• Middle Aged
• Paclitaxel (adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)
• Treatment Failure