A phase I trial of perillyl alcohol administered four times daily for 14 days out of 28 days.

Purpose: Perillyl alcohol (POH) has been shown to have both chemopreventative and chemotherapeutic activities in preclinical studies. The underlying mechanism(s) of action of POH have yet to be delineated but may involve effects on the transforming growth factor beta (TGFbeta) and/or the Ras signaling pathways. A phase I study of POH for 14 days out of every 28 days in subjects with advanced malignancies was performed to evaluate dose escalation, toxicity, pharmacokinetics, and effects on TGFbeta and Ras.

Gemcitabine, Paclitaxel, and piritrexim: a phase I study.

Piritrexim is a new antifolate that has shown activity in methotrexate-resistant tumors. Gemcitabine is an antimetabolite similar in structure to cytosine arabinoside with early studies demonstrating activity in a variety of cancers. It also has apparent synergistic activity with antifolates from initial work in tumor models.

Phase I pharmacokinetic and pharmacodynamic study of recombinant human endostatin in patients with advanced solid tumors.

Purpose: Endostatin is the first endogenous angiogenesis inhibitor to enter clinical trials. Laboratory investigations with endostatin have indicated broad antitumor activity coupled with remarkably low toxicity. A phase I trial of recombinant human endostatin was designed to evaluate toxicity and explore biologic effectiveness in patients with refractory solid tumors.

Phase I study of eniluracil, oral 5-fluororacil and gemcitabine in patients with advanced malignancy.

Purpose: The objectives of this trial were to assess the maximal tolerated dose and toxicity of the combination of oral eniluracil and 5-fluorouracil and intravenous gemcitabine.

Patients And Methods: Patients with histologically confirmed, incurable malignancy (solid tumor or lymphoma) refractory to standard therapy or for which no standard therapy exists were enrolled. The treatment plan consisted of weekly gemcitabine for three weeks with twice daily dosing of 5-FU and eniluracil for 21 days beginning on day one of gemcitabine.

Phase I and pharmacokinetic study of a micronized formulation of carboxyamidotriazole, a calcium signal transduction inhibitor: toxicity, bioavailability and the effect of food.

Purpose: This Phase I study was conducted to evaluate the toxicity profile and determine the maximum tolerated dose (MTD) of an oral micronized formulation of the signal transduction inhibitor carboxyamidotriazole (CAI). Bioavailability of the micronized formulation relative to a gelatin capsule (gelcap) formulation was assessed. The effects of food intake and timing on CAI steady-state plasma concentrations (C(ss)) were also investigated.