title: Optimized sequence of drug administration and schedule leads to improved dose delivery for gemcitabine and paclitaxel in combination: a phase I trial in patients with recurrent ovarian cancer.
abstract: We examined appropriate sequence, schedule, and doses of gemcitabine (G) and paclitaxel (T) in patients with persistent or recurrent epithelial ovarian cancer. Patients received a maximum of six cycles of gemcitabine on days 1 and 8 (starting 1000 mg/m(2)), and paclitaxel (starting 135 mg/m(2)) on day 8 (groups A and B) or day 1 (group C). Drug sequences (G-->T and T-->G) were tested in group A. In group A, changing sequences of gemcitabine and paclitaxel infusion were evaluated. Sequence G-->T raised grade 3 alanine transaminase in two of three patients leading to use of T-->G sequence for remainder of study. In group B, maximum tolerable dose was reached at gemcitabine 1000 mg/m(2) and paclitaxel 175 mg/m(2). Reducing paclitaxel to 150 mg/m(2) allowed escalation of gemcitabine to 1250 mg/m(2), but neutropenia-related treatment delays occurred. Giving paclitaxel on day 1 (group C) enabled administration of paclitaxel 175 mg/m(2) and gemcitabine 1250 mg/m(2) with minimal dose adjustments. The overall response rate was 41.0%, with 2 complete responses and 14 partial responses in 39 eligible patients. The schedule of paclitaxel 175 mg/m(2) (day 1) and gemcitabine 1250 mg/m(2) (days 1 and 8), with sequence of T-->G, appears most suitable with tolerable toxicity and promising activity.
authors: CR UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom. c.j.poole@bham.ac.uk
authors: C J
authors: CJ
authors: Poole
authors: T
authors: T
authors: Perren
authors: S
authors: S
authors: Gawande
authors: M
authors: M
authors: Ridderheim
authors: J
authors: J
authors: Cook
authors: A
authors: A
authors: Jenkins
authors: D
authors: D
authors: Roychowdhury