Congress Abstracts 2003

97

A PHASE I/II STUDY OF XYOTAX™ (CT-2103), A TUMOR-TARGETED TAXANE, IN PATIENTS WITH RECURRENT OVARIAN CANCER. Cheri Graham, RN, BSN, Gynecologic Oncology Associates, Newport Beach, CA; Paul Sabbatini, MD, Memorial Sloan-Kettering Cancer Center, New York, NY; John Brown, MD, Gynecologic Oncology Associates, Newport Beach, CA; and Mary Bolton, MD, PhD, Cell Therapeutics, Inc., Seattle, WA.

Xyotax is a novel taxane designed to concentrate selectively in tumors and result in superior efficacy, safety, and symptom control, compared to standard taxane therapy. Conjugation of paclitaxel to poly-L-glutamate (a chain of a naturally occurring amino acids) enhances aqueous solubility and eliminates the need for the toxic solubilizing agent, Cremophor. Xyotax was evaluated in a multicenter phase I/II study of patients with heavily pretreated recurrent ovarian cancer; this study is now closed to enrollment. Ninety-nine patients received 1 to 11 cycles of Xyotax, each cycle administered as a 10-minute infusion, via a peripheral vein, at a dose of 175 mg/m2 conjugated paclitaxel every 21 days. Forty two percent of the patients received less than or equal to 4 cycles. Twelve patients remain on the study. The median number of prior regimens is 3 (range, 1–10). The data available to date are: PR in 9 patients, SD in 35 patients, and PD in 44 patients. As of July 2002, the 6-month survival rate was 92%. No baldness has been observed, and only 4 patients have developed mild hair thinning. Hypersensitivity reactions (HSRs), which occurred in only 10% of patients, were easily managed with steroid/antihistamine therapy. Many of these patients continued to receive additional cycles of the study drug with premedications to prevent recurrent HSRs. Only 2 patients discontinued the study due to HSRs. The routine use of steroid, antihistamine, and antiemetic premedications is not required in most patients. Almost all reported adverse events have been mild to moderate. Grade 3 (severe) drug-related events reported to date are leukopenia, neutropenia, neuropathy (4 patients each), HSRs (2 patients), and fatigue (1 patient). No drug-related grade 4 events have been reported. Response rates and times-to-progression for patients with platinum-resistant and platinum-sensitive disease will be presented separately. The promising activity and good tolerability of Xyotax seen in these heavily pretreated patients has prompted CTI to initiate a phase III trial of Xyotax for the first-line treatment of ovarian cancer.