""""""""The phase I clinical trial of CAI has been closed to accrual and some patients remain on treatment. Of the three formulations tested, the micronized powder encapsulated formulation has been chosen for phase II study and is being now used for our Phase II clinical trial of CAI for relapsed epithelial ovarian cancer patients. This formulation is ~50% bioavailable compared to the liquid formulation, but with a more favorable toxicity profile. The frequency and severity of nausea, vomiting, and anorexia are less, with no altered taste or peripheral neuropathy noted. Disease stabilization has been observed in ~49% of pts treated on the phase I clinical trial, with disease stabilization for up to 10 months in ovarian cancer patients and up to15 mo in our institution and longer in the other phase I trial at the U-Wisc. Studies of dosing time and food demonstrated that food increases the Cmax of CAI up to 6-fold, thus recommendations are for first am dosing or immediately before bed. A 250 mg/evening dose is recommended for outside studies. We are using a pharmacokinetically dosed approach for the ovarian cancer phase II study. A phase II clinical trial of single agent CAI for pts with hormone-refractory prostate cancer has been completed without prolongation of disease stabilization. Only patients with measurable disease, and thus a large tumor burden, were eligible due to the finding that CAI reduces PSA excretion from prostate cancer cells in vitro. The phase I trial of CAI with paclitaxel remains open. Partial and minor responses have been observed in fallopian tube, renal cell, and lung cancers, and melanoma. Several patients at the highest doses of paclitaxel have required G-CSF because their AGC did not recover within the14 d period between paclitaxel administration and CAI dosing for the next cycle. Pharmacokinetic studies identified an increase in CAI plasma concentration after paclitaxel administration. The protocol is being amended for daily CAI treatment to provide continuous exposure to CAI. New studies are ongoing with collaborators that have identified an anti-angiogenic activity of CAI in ocular models. Clinical trial preparation is underway in collaboration with the NEI for studies in age-related macular degeneration.""""""""
Showing the most recent 10 out of 23 publications
