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


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.
Ramanathan
Ramesh K
RK
Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. ramanathanrk@upmc.edu
Picus
Joel
J
Raftopoulos
Haralambos
H
Bernard
Stephen
S
Lockhart
A Craig
AC
Frenette
Gary
G
Macdonald
John
J
Melin
Susan
S
Berg
Daniel
D
Brescia
Frank
F
Hochster
Howard
H
Cohn
Allen
A
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001772:Blood Cell Count; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017211:Treatment Failure
D000972:Antineoplastic Agents, Phytogenic; C479501:MAC321; D017239:Paclitaxel