Detail of "219989-84-1"

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Phase I Clinical Trial of BMS-247550, A Derivative of Epothilone B, Using Accelerated Titration 2B Design

Phase I Clinical Trial of BMS-247550, A Derivative of Epothilone B, Using Accelerated Titration 2B Design. Gadgeel, Shirish M.; Wozniak, Antoinette; Boinpally, Ramesh R.; Wiegand, Richard; Heilbrun, Lance K.; Jain, Vikas; Parchment, Ralph; Colevas, Dimitrios; Cohen, Marvin B.; LoRusso, Patricia M. (Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA). Clinical Cancer Research, 11(17), 6233-6239 (English) 2005 American Association for Cancer Research. CODEN: CCREF4. ISSN: 1078-0432. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Purpose: BMS-247550 is a semisynthetic deriv. of epothilone B with mechanism of action analogous to paclitaxel. It has shown impressive antitumor activity in preclin. studies including in taxane-resistant models. We conducted a phase I trial, based on accelerated titrn. "2B" design, of BMS-247550 given as a 1-h infusion every 3 wk. Exptl. Design: Seventeen patients (M:F, ; median age, 54 years; performance status, 0-2) were treated on the trial. Forty-five cycles (1-9 cycles) of BMS-247550 were given at dosages ranging from 7.4 to 56 mg/m2. All patients received prophylaxis for hypersensitivity reactions, related to Cremophor-EL, with steroids and histamine antagonists. Results: First-course dose-limiting toxicity (DLT) was obsd. in two of three patients at 56 mg/m2 (neutropenic sepsis, prolonged grade 4 neutropenia) and in one of six patients at 40 mg/m2. Nonhematol. grade 3 to 4 toxicities obsd. were emesis and fatigue and they occurred only at 56 mg/m2. Grade 1 to 2 peripheral neuropathy was also obsd. Other grade 1 to 2 toxicities were myalgias, arthralgias, rash, hand/ft syndrome, and mucositis. AUC and Cmax seemed proportional to the dose and the DLT. Development of neutropenia with BMS-247550 is related to the duration of drug exposure above a threshold. Conclusions: The max. tolerated dose (MTD) of BMS-247550 is 40 mg/m2 given every 3 wk. Neutropenia is the DLT. The accelerated titrn. "2B" design may help in detg. MTD with fewer patients enrolled and more being treated closer to the MTD. However, the accelerated titrn.Except for chemicals metioned above, 219989-84-1 and 152044-54-7 are also used. design did not seem to shorten the study duration. .

Phase II trial of ixabepilone, an epothilone B analog, given daily for three days every three weeks, in metastatic breast cancer

All Rights Reserved. Phase II trial of ixabepilone, an epothilone B analog, given daily for three days every three weeks, in metastatic breast cancer. Denduluri, Neelima; Lee, James J.; Walshe, Janice; Berman, Arlene W.; Vatas, Ujala; Chow, Catherine K.; Steinberg, Seth M.; Cox, Michael C.; Low, Jennifer A.; Swain, Sandra M. (Center for Cancer Research, National Cancer Institute, Breast Cancer Section, Medical Oncology Branch, National Institutes of Heath, Bethesda, MD 20889-5015, USA). Investigational New Drugs, Volume Date 2007, 25(1), 63-67 (English) 2006 Springer.Several reagents such as 219989-84-1 is used here. CODEN: INNDDK. ISSN: 0167-6997. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Twelve patients with metastatic breast cancer previously exposed to taxanes were treated on a Phase II trial with ixabepilone. Eligible patients had histol. confirmed metastatic breast cancer with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST), and adequate hematopoietic, renal, and hepatic function. Ixabepilone 8 mg/m2/day was given i.v. daily for 3 days for the first 3-wk cycle and increased to 10 mg/m2/day for subsequent cycles if patients did not have hematol. or other toxicity after the first cycle. Patients continued treatment until progressive disease or unacceptable toxicity. Three, 29, and 33 of 65 cycles administered were at the 7 mg/m2, 8 mg/m2 and 10 mg/m2 dose levels resp. Grade 4 leukopenia (n=1), grade 3 neutropenia (n=2), grade 2 neuropathy (n=3), and grade 2 transaminase elevation (n=2) were the most notable toxicities. Ten patients had stable disease for at least 6 wk. No complete or partial responses were obsd. in 12 evaluable patients treated with ixabepilone daily for 3 days. Although ixabepilone was well-tolerated, the dose of 8-10 mg/m2 daily for 3 days is not an effective therapy in metastatic breast cancer previously exposed to taxanes. .