Randomized Crossover Pharmacokinetic Study of Solvent-Based Paclitaxel and nab-Paclitaxel

• Published in: Clinical cancer research Vol. 14; no. 13; pp. 4200 - 4205
• Main Authors: GARDNER, Erin R, DAHUT, William L, SCRIPTURE, Charity D, JONES, Jacquin, ARAGON-CHING, Jeanny B, DESAI, Neil, HAWKINS, Michael J, SPARREBOOM, Alex, FIGG, William D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.07.2008
• Subjects: Adult; Aged; Albumins - pharmacokinetics; Albumins - therapeutic use; anoparticle; Antineoplastic agents; Antineoplastic Agents, Phytogenic - pharmacokinetics; Biological and medical sciences; Breast Neoplasms - drug therapy; Carcinoma - drug therapy; Cross-Over Studies; Fallopian Tube Neoplasms - drug therapy; Female; Humans; Male; Medical sciences; Middle Aged; Ovarian Neoplasms - drug therapy; Paclitaxel - pharmacokinetics; Paclitaxel - therapeutic use; pharmacokinetics; Pharmacology. Drug treatments; Prostatic Neoplasms - drug therapy; Solvents - chemistry; taxane; Antineoplastic agent; Organic solvent; Randomization; Taxane derivatives; Paclitaxel; Pharmacokinetics; Antimitotic; Crossover study
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-4592

Purpose: Abraxane (ABI-007) is a 130-nm albumin-bound ( nab ) particle formulation of paclitaxel, devoid of any additional excipients. We hypothesized that this change in formulation alters the systemic disposition of paclitaxel compared with conventional solvent-based formulations (sb-paclitaxel; Taxol), and leads to improved tolerability of the drug. Patients and Methods: Patients with malignant solid tumors were randomized to receive the recommended single-agent dose of nab -paclitaxel (260 mg/m 2 as a 30-minute infusion) or sb-paclitaxel (175 mg/m 2 as a 3-hour infusion). After cycle 1, patients crossed over to the alternate treatment. Pharmacokinetic studies were carried out for the first cycle of sb-paclitaxel and the first two cycles of nab -paclitaxel. Results: Seventeen patients were treated, with 14 receiving at least one cycle each of nab -paclitaxel and sb-paclitaxel. No change in nab -paclitaxel pharmacokinetics was found between the first and second cycles ( P = 0.95), suggesting limited intrasubject variability. Total drug exposure was comparable between the two formulations ( P = 0.55) despite the dose difference. However, exposure to unbound paclitaxel was significantly higher after nab -paclitaxel administration, due to the increased free fraction (0.063 ± 0.021 versus 0.024 ± 0.009; P < 0.001). Conclusion: This study shows that paclitaxel disposition is subject to considerable variability depending on the formulation used. Because systemic exposure to unbound paclitaxel is likely a driving force behind tumoral uptake, these findings explain, at least in part, previous observations that the administration of nab -paclitaxel is associated with augmented antitumor efficacy compared with solvent-based paclitaxel.