PT  - JOURNAL ARTICLE
AU  - Ibrahim, Nuhad K.
AU  - Desai, Neil
AU  - Legha, Sewa
AU  - Soon-Shiong, Patrick
AU  - Theriault, Richard L.
AU  - Rivera, Edgardo
AU  - Esmaeli, Bita
AU  - Ring, Sigrid E.
AU  - Bedikian, Agop
AU  - Hortobagyi, Gabriel N.
AU  - Ellerhorst, Julie A.
TI  - Phase I and Pharmacokinetic Study of ABI-007, a Cremophor-free, Protein-stabilized, Nanoparticle Formulation of Paclitaxel
DP  - 2002 May 01
TA  - Clinical Cancer Research
PG  - 1038--1044
VI  - 8
IP  - 5
4099  - http://clincancerres.aacrjournals.org/content/8/5/1038.short
4100  - http://clincancerres.aacrjournals.org/content/8/5/1038.full
SO  - Clin Cancer Res2002 May 01; 8
AB  - 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 Cmax and area under the curveinf values to increase linearly over the ABI-007 dose range of 135–300 mg/m2. Cmax and area under the curveinf 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.