Phase I and Pharmacokinetic Study of ABI-007, a Cremophor-free, Protein-stabilized, Nanoparticle Formulation of Paclitaxel

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 pe...

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Bibliographic Details
Published in:Clinical cancer research 2002-05, Vol.8 (5), p.1038-1044
Main Authors: IBRAHIM, Nuhad K, DESAI, Neil, ELLERHORST, Julie A, LEGHA, Sewa, SOON-SHIONG, Patrick, THERIAULT, Richard L, RIVERA, Edgardo, ESMAELI, Bita, RING, Sigrid E, BEDIKIAN, Agop, HORTOBAGYI, Gabriel N
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Albumin-Bound Paclitaxel
Albumins - chemistry
Antineoplastic agents
Antineoplastic Agents, Phytogenic - adverse effects
Antineoplastic Agents, Phytogenic - pharmacokinetics
Antineoplastic Agents, Phytogenic - therapeutic use
Area Under Curve
Biological and medical sciences
Castor Oil - analogs & derivatives
Castor Oil - chemistry
Chemistry, Pharmaceutical
Chemotherapy
Diarrhea - chemically induced
Dose-Response Relationship, Drug
Female
Humans
Male
Medical sciences
Metabolic Clearance Rate
Middle Aged
Nausea - chemically induced
Neoplasms - drug therapy
Neoplasms - metabolism
Neoplasms - pathology
Nervous System Diseases - chemically induced
Paclitaxel - adverse effects
Paclitaxel - analogs & derivatives
Paclitaxel - chemistry
Paclitaxel - pharmacokinetics
Paclitaxel - therapeutic use
Particle Size
Pharmacology. Drug treatments
Stomatitis - chemically induced
Taxoids
Treatment Outcome
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Summary: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/m 2 (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/m 2 ), consisted of sensory neuropathy (3 patients), stomatitis (2 patients), and superficial keratopathy (2 patients). The MTD was thus determined to be 300 mg/m 2 (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/m 2 . 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.
ISSN:1078-0432
1557-3265