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Medline ® Abstract for Reference 121

of 'Infusion reactions to systemic chemotherapy'

121
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Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel.
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Ibrahim NK, Desai N, Legha S, Soon-Shiong P, Theriault RL, Rivera E, Esmaeli B, Ring SE, Bedikian A, Hortobagyi GN, Ellerhorst JA
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Clin Cancer Res. 2002;8(5):1038.
 
PURPOSE: ABI-007 is a novel Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. The absence of Cremophor EL may permit ABI-007 to be administered without the premedications used routinely for the prevention of hypersensitivity reactions. Furthermore, this novel formulation permits a higher paclitaxel concentration in solution and, thus, a decreased infusion volume and time. This Phase I study examines the toxicity profile, maximum tolerated dose (MTD), and pharmacokinetics of ABI-007.
EXPERIMENTAL DESIGN: ABI-007 was administered in the outpatient setting, as a 30-min infusion without premedications. Doses of ABI-007 ranged from 135 (level 0) to 375 mg/m2 (level 3). Sixteen patients participated in pharmacokinetic studies.
RESULTS: Nineteen patients were treated. No acute hypersensitivity reactions were observed during the infusion period. Hematological toxicity was mild and not cumulative. Dose-limiting toxicity, which occurred in 3 of 6 patients treated at level 3 (375 mg/m2), consisted of sensory neuropathy (3 patients), stomatitis (2 patients), and superficial keratopathy (2 patients). The MTD was thus determined to be 300 mg/m2 (level 2). Pharmacokinetic analyses revealed paclitaxel C(max) and area under the curve(inf) values to increase linearly over the ABI-007 dose range of 135-300 mg/m2. C(max) and area under the curve(inf) values for individual patients correlated well with toxicity.
CONCLUSIONS: ABI-007 offers several features of clinical interest, including rapid infusion rate, absence of requirement for premedication, and a high paclitaxel MTD. Our results provide support for Phase II trials to determine the antitumor activity of this drug.
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Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
PMID