TY - JOUR
T1 - A phase II study of milataxel
T2 - A novel taxane analogue in previously treated patients with advanced colorectal cancer
AU - Ramanathan, Ramesh K.
AU - Picus, Joel
AU - Raftopoulos, Haralambos
AU - Bernard, Stephen
AU - Lockhart, A. Craig
AU - Frenette, Gary
AU - Macdonald, John
AU - Melin, Susan
AU - Berg, Daniel
AU - Brescia, Frank
AU - Hochster, Howard
AU - Cohn, Allen
N1 - Funding Information:
Supported by a grant from Wyeth Research, Philadelphia, PA.
PY - 2008/3
Y1 - 2008/3
N2 - 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.
AB - 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.
KW - Colorectal cancer
KW - MAC-321
KW - Milataxel
KW - Phase II
KW - Taxanes
UR - http://www.scopus.com/inward/record.url?scp=37249024710&partnerID=8YFLogxK
U2 - 10.1007/s00280-007-0489-5
DO - 10.1007/s00280-007-0489-5
M3 - Article
C2 - 17516069
AN - SCOPUS:37249024710
SN - 0344-5704
VL - 61
SP - 453
EP - 458
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 3
ER -