TY - JOUR
T1 - Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel
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.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2002/5
Y1 - 2002/5
N2 - 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) MWM2), 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 Cmaxand area under the curveinfvalues to increase linearly over the ABI-007 dose range of 135-300 mg/m2Cmaxand area under the curveinfvalues 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.
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) MWM2), 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 Cmaxand area under the curveinfvalues to increase linearly over the ABI-007 dose range of 135-300 mg/m2Cmaxand area under the curveinfvalues 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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M3 - Article
C2 - 12006516
AN - SCOPUS:0036096946
SN - 1078-0432
VL - 8
SP - 1038
EP - 1044
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 5
ER -