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A Phase I clinical trial of ixabepilone (BMS‐247550), an epothilone B analog, administered intravenously on a daily schedule for 3 days
Author(s) -
Zhuang Sen H.,
Agrawal Manish,
Edgerly Maureen,
Bakke Susan,
Kotz Herb,
Thambi Paul,
Rutt Ann,
Balis Frank M.,
Bates Susan,
Fojo Tito
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20977
Subject(s) - medicine , ixabepilone , neutropenia , tolerability , febrile neutropenia , epothilone , hyponatremia , adverse effect , toxicity , gastroenterology , anesthesia , cancer , metastatic breast cancer , breast cancer , biology , genetics
BACKGROUND The epothilones are a novel class of microtubule‐stabilizing agents. Ixabepilone (BMS‐247550; NSC 710428) is a semisynthetic analog of the natural product epothilone B. The authors conducted a Phase I study by administering ixabepilone to patients as a 1‐hour intravenous infusion daily for 3 consecutive days every 21 days. METHODS Twenty‐six patients were enrolled and received ixabepilone at a starting dose of 8 or 10 mg/m 2 per day for 3 consecutive days. RESULTS One hundred and nineteen cycles were administered to 26 patients. The maximum‐tolerated dose was 8 mg/m 2 per day of ixabepilone administered as a 1‐hour intravenous infusion daily for 3 consecutive days every 21 days. The dose‐limiting toxicity (DLT) was neutropenia. Other nonhematologic Grade 3 toxicities included fatigue (3 cycles), hyponatremia (1 cycle), anorexia (1 cycle), ileus (1 cycle), stomatitis (1 cycle), and emesis (1 cycle). Prolonged disease stabilization was observed in patients with mesothelioma, ovarian carcinoma, and renal cell carcinoma. CONCLUSIONS The recommended Phase II dose of ixabepilone on the daily schedule for 3 days was 8–10 mg/m 2 per day. Neutropenia was the DLT. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting. Cancer 2005. Published 2005 by the American Cancer Society.