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Randomized Controlled Trial
. 2008 Jul 1;14(13):4200-5.
doi: 10.1158/1078-0432.CCR-07-4592.

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel

Erin R Gardner  1 , William L Dahut, Charity D Scripture, Jacquin Jones, Jeanny B Aragon-Ching, Neil Desai, Michael J Hawkins, Alex Sparreboom, William D Figg
Affiliations
Randomized Controlled Trial

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel

Erin R Gardner et al. Clin Cancer Res. .

Abstract

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.

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Figures

Figure 1
Figure 1
Unbound paclitaxel concentration-time profiles following nab-paclitaxel (A) or sb-paclitaxel (B) administration, for all 14 individuals.
See this image and copyright information in PMC

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