A phase I and pharmacokinetic study of oral perifosine with different loading schedules in patients with refractory neoplasms.

Purpose: To determine the maximum tolerated dose (MTD) of perifosine (NSC 639966), an alkylphospholipid modulator of signal transduction, using different oral loading and maintenance regimens in an effort to avoid gastrointestinal toxicity while seeking maximal sustained plasma concentrations.

Methods: Thirty-one patients with advanced neoplasms were treated with monthly cycles of perifosine loading doses of 300, 600, 900, 1,200 and 1,500 mg (dose levels 1 through 5, respectively) on days 1-2 depending on the actual dose of the initial cycle. For subsequent cycles, perifosine loading doses were reduced to 100, 200, 300, 400 and 1,000 mg at the respective corresponding dose levels.

A randomized phase 2 trial comparing 3-hour versus 96-hour infusion schedules of paclitaxel for the treatment of metastatic breast cancer.

Background: This study was performed to compare efficacy and toxicity profiles of paclitaxel using 3-hour versus 96-hour infusion schedules.

Methods: Patients with metastatic breast cancer (MBC) were randomly assigned to receive paclitaxel starting at a dose of 250 mg/m(2) intravenously (iv) over 3 hours every 21 days or paclitaxel starting at a dose of 140 mg/m(2) iv over 96 hours every 21 days. Stratification variables included number of prior chemotherapy regimens and previous response to anthracyclines.

New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

Background: Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.

Clinical trial endpoints in ovarian cancer: report of an FDA/ASCO/AACR Public Workshop.

Objective: The unique characteristics of cancer, particularly issues involving the use of surrogate endpoints in clinical trials, present special challenges in the development of cancer drugs. In response, the U.S.

Clinical pharmacology of flavopiridol following a 72-hour continuous infusion.

Background: Flavopiridol, a novel flavone derivative, inhibits cyclin-dependent kinase-1. We initiated a Phase I trial in patients with refractory solid tumors to determine the maximum tolerated dose and characterize the adverse effect profile.

Objective: To characterize the clinical pharmacology of flavopiridol.