Paclitaxel is an
anticancer agent effective for the treatment of breast, ovarian, lung, and
head and neck cancer. Because of water insolubility,
paclitaxel is formulated with the
micelle-forming vehicle
Cremophor EL to enhance
drug solubility. However, the addition of
Cremophor EL results in
hypersensitivity reactions, neurotoxicity, and altered pharmacokinetics of
paclitaxel. To circumvent these unfavorable effects resulting from the addition of
Cremophor EL, efforts have been made to develop new delivery systems for
paclitaxel administration. For example,
ABI-007 is a
Cremophor-free,
albumin-stabilized, nanoparticle
paclitaxel formulation that was found to have significantly less toxicity than
Cremophor-containing
paclitaxel in mice. Pharmacokinetic studies indicate that in contrast to
Cremophor-containing
paclitaxel,
ABI-007 displays linear pharmacokinetics over the clinically relevant dose range of 135-300 mg/m(2). In a phase III study conducted in patients with metastatic
breast cancer, patients treated with
ABI-007 achieved a significantly higher objective response rate and time to progression than those treated with
Cremophor-containing
paclitaxel. Together these findings suggest that nanoparticle
albumin-bound paclitaxel may enable clinicians to administer
paclitaxel at higher doses with less toxicity than is seen with
Cremophor-containing
paclitaxel. The role of this novel
paclitaxel formulation in combination
therapy with other
antineoplastic agents needs to be determined.