BACKGROUND: The epothilone B analog, BMS-247550, is a non-taxane microtubulin-stabilizing agent with preclinical activity in taxane-resistant cell lines and phase I activity in colorectal cancer. We conducted a phase II study of single-agent BMS-247550 in advanced colorectal cancer patients who had disease progression following treatment with irinotecan-5-fluorouracil-leucovorin (IFL). PATIENTS AND METHODS: Patients were required to have histologically or cytologically confirmed advanced or metastatic colorectal cancer; progressed on or after chemotherapy with IFL; Eastern Cooperative Oncology Group performance status < or =1; peripheral neuropathy grade < or =1; and adequate laboratory parameters. BMS-247550 40 mg/m(2) was administered intravenously over 3 h every 3 weeks. Patients were evaluated for response every 6 weeks. RESULTS: Twenty-five patients were enrolled; all were evaluable for toxicity and 23 were evaluable for response. There were no complete or partial responses. Thirteen patients (56%) had stable disease after two cycles of therapy; five patients (20%) received six or more cycles. The median time to progression was 11 weeks; median overall survival was 36 weeks. There was considerable grade 3/4 hematological toxicity, including neutropenia (48%) and leukopenia (36%). Grade 3/4 non-hematological toxicities included grade 3 hypersensitivity reaction (12%) and peripheral neuropathy (20%). CONCLUSIONS: Single-agent BMS-247550 (40 mg/m(2)) administered every 21 days demonstrated no activity in advanced colorectal cancer. Peripheral neuropathy was treatment-limiting.
BACKGROUND: The epothilone B analog, BMS-247550, is a non-taxane microtubulin-stabilizing agent with preclinical activity in taxane-resistant cell lines and phase I activity in colorectal cancer. We conducted a phase II study of single-agent BMS-247550 in advanced colorectal cancerpatients who had disease progression following treatment with irinotecan-5-fluorouracil-leucovorin (IFL). PATIENTS AND METHODS: Patients were required to have histologically or cytologically confirmed advanced or metastatic colorectal cancer; progressed on or after chemotherapy with IFL; Eastern Cooperative Oncology Group performance status < or =1; peripheral neuropathy grade < or =1; and adequate laboratory parameters. BMS-247550 40 mg/m(2) was administered intravenously over 3 h every 3 weeks. Patients were evaluated for response every 6 weeks. RESULTS: Twenty-five patients were enrolled; all were evaluable for toxicity and 23 were evaluable for response. There were no complete or partial responses. Thirteen patients (56%) had stable disease after two cycles of therapy; five patients (20%) received six or more cycles. The median time to progression was 11 weeks; median overall survival was 36 weeks. There was considerable grade 3/4 hematological toxicity, including neutropenia (48%) and leukopenia (36%). Grade 3/4 non-hematological toxicities included grade 3 hypersensitivity reaction (12%) and peripheral neuropathy (20%). CONCLUSIONS: Single-agent BMS-247550 (40 mg/m(2)) administered every 21 days demonstrated no activity in advanced colorectal cancer. Peripheral neuropathy was treatment-limiting.
Authors: Jason Konner; Rachel N Grisham; Jae Park; Owen A O'Connor; Gillian Cropp; Robert Johnson; Alison L Hannah; Martee L Hensley; Paul Sabbatini; Svetlana Mironov; Svetlana Miranov; Samuel Danishefsky; David Hyman; David R Spriggs; Jakob Dupont; Carol Aghajanian Journal: Invest New Drugs Date: 2011-11-10 Impact factor: 3.850
Authors: Neelima Denduluri; James J Lee; Janice Walshe; Arlene W Berman; Ujala Vatas; Catherine K Chow; Seth M Steinberg; Michael C Cox; Jennifer A Low; Sandra M Swain Journal: Invest New Drugs Date: 2006-08-25 Impact factor: 3.850
Authors: B Melichar; E Casado; J Bridgewater; J Bennouna; M Campone; P Vitek; J-P Delord; J Cerman; R Salazar; J Dvorak; C Sguotti; P Urban; K Viraswami-Appanna; E Tan; J Tabernero Journal: Br J Cancer Date: 2011-10-25 Impact factor: 7.640
Authors: Patrick A Ott; Anne Hamilton; Amanda Jones; Naomi Haas; Tsiporah Shore; Sandra Liddell; Paul J Christos; L Austin Doyle; Michael Millward; Franco M Muggia; Anna C Pavlick Journal: PLoS One Date: 2010-01-20 Impact factor: 3.240