PHILADELPHIAEncapsulating paclitaxel (Taxol) in liposomes
almost eliminates nonhematologic toxicities such as neuropathy and
greatly prolongs the drugs half-life, Joseph Treat, MD,
reported at the clinical investigators workshop. Dr. Treat is
Vice Chairman of the Department of Medical Oncology at Fox Chase
Cancer Center and Medical Director of the Temple University Cancer
Center in Philadelphia. The workshop was sponsored by the University
of Texas M.D. Anderson Cancer Center and by Pharmacia Oncology.
Paclitaxel is poorly soluble, and the usual formulation
requires Cremophor for human administration, Dr. Treat said.
Potential advantages of liposomal encapsulated paclitaxel
include elimination of toxicities related to Cremophor, reduction of
infusion time, and preservation of the anti-tumor effect while
reducing side effects such as neurotoxicity, myalgia, arthralgia, and alopecia.
Improved Toxicity Profile
Dr. Treat discussed a phase I trial of liposomal encapsulated
paclitaxel (LEP). At the recommended phase II dose of 175 mg/m²,
the main toxicity was grade 3-4 neutropenia, which Dr. Treat pointed
out is also a problem with conventional paclitaxel. There was minimal
alopecia at this level. Higher doses caused unacceptable levels of
mucositis and neutropenia. There were no significant
neurotoxicities seen at any of the doses tested, Dr. Treat
said. The toxicity profile is quite different from conventional
paclitaxel. The elimination of Cremophor also means that this
formulation has linear pharmacokinetics and a prolonged terminal
half-life of about 38 hours.
Preliminary efficacy data showed two partial responses among the 30
patients in the phase I trial: one with nonsmall-cell lung
cancer and one with breast cancer with liver and soft-tissue