Multicenter Phase II Trial of ABI-007, an Albumin- Bound Paclitaxel, in Women With Metastatic Breast Cancer Nuhad K. Ibrahim, Brian Samuels, Ray Page, Dinesh Doval, Kirtikumar M. Patel, S.C. Rao, Madhavan Krishnan Nair, Paul Bhar, Neil Desai, and Gabriel N. Hortobagyi A B S T R A C T Purpose ABI-007 is a novel nanoparticle, albumin-bound paclitaxel that is free of solvents. This multicenter phase II study was designed to evaluate the efficacy and safety of ABI-007 for the treatment of metastatic breast cancer (MBC). Patients and Methods Sixty-three women with histologically confirmed and measurable MBC received 300 mg/m 2 ABI-007 by intravenous infusion over 30 minutes every 3 weeks without premedication. Forty-eight patients received prior chemotherapy; 39 patients received no prior treatment for metastatic disease. Results Overall response rates (complete or partial responses) were 48% (95% CI, 35.3% to 60.0%) for all patients. For patients who received ABI-007 as first-line and greater than first-line therapy for their metastatic disease, the respective response rates were 64% (95% CI, 49.0% to 79.2%) and 21% (95% CI, 7.1% to 42.1%). Median time to disease progression was 26.6 weeks, and median survival was 63.6 weeks. No severe hypersensitivity reactions were reported despite the lack of premedication. Toxicities observed were typical of paclitaxel and included grade 4 neutropenia (24%), grade 3 sensory neuropathy (11%), and grade 4 febrile neutropenia (5%). Patients received a median of six treatment cycles; 16 patients had 25% dose reductions because of toxicities, and two of these patients had subsequent dose reductions. Conclusion ABI-007, the first biologically interactive albumin-bound form of paclitaxel in the nanoparticle state, uses the natural carrier albumin rather than synthetic solvents to deliver paclitaxel and allows for safe administration of high paclitaxel doses without premedication, resulting in significant antitumor activity in patients with MBC, including those receiving the drug as first-line therapy. J Clin Oncol 23:6019-6026. © 2005 by American Society of Clinical Oncology INTRODUCTION Breast cancer, the most common malignancy in women, continues to be a major health con- cern. Almost one third of all cancers in women are breast cancer, and the disease is expected to kill an estimated 40,110 women in the United States in 2004. 1 Treatments for early-stage dis- ease have improved survival, and improve- ments in chemotherapies have shown demonstrable benefit for women with meta- static breast cancer (MBC). 2,3 Paclitaxel plays a central role in the treatment of MBC. 4 However, its use is lim- ited by its poor solubility and the toxicities associated with Cremophor EL (polyethoxy- lated castor oil), the lipid-based solvent used as a vehicle for Taxol (Bristol-Myers Squibb From The University of Texas M.D. Anderson Cancer Center, Houston, TX; Lutheran General Cancer Center, Park Ridge, IL; The Center for Cancer and Blood Disorders, Fort Worth, TX; Rajiv Gandhi Cancer Institute, New Delhi, India; Gujarat Cancer Research Insti- tute, Ahmedabad, India; MNJ Institute of Oncology, Hyderabad, India; Regional Cancer Center, Thiruvananthapuram, India; and American BioScience Inc, Santa Monica, CA. Submitted November 3, 2004; accepted May 11, 2005. Sponsored by American BioScience, Inc, Santa Monica, CA. Presented in part at the 25th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 11-14, 2002; and the 38th Annual Meeting of the American Society of Clinical Oncol- ogy, Orlando, FL, May 18-21, 2002. Authors’ disclosures of potential con- flicts of interest are found at the end of this article. Address reprint requests to Nuhad K. Ibrahim, MD, Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 424, Houston, TX 77030-4009; e-mail: nibrahim@mdanderson.org. © 2005 by American Society of Clinical Oncology 0732-183X/05/2325-6019/$20.00 DOI: 10.1200/JCO.2005.11.013 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 23  NUMBER 25  SEPTEMBER 1 2005 6019 Downloaded from ascopubs.org by 3.84.155.67 on June 12, 2022 from 003.084.155.067 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.