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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
  1. C. J. Poole*,§,
  2. T. Perren,
  3. S. Gawande,
  4. M. Ridderheim,
  5. J. Cook§,
  6. A. Jenkins and
  7. D. Roychowdhury
  1. *CR UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom
  2. St James University Hospital, Leeds, United Kingdom
  3. Eli Lilly and Company, Indianapolis, Indiana
  4. §City Hospital, Birmingham, United Kingdom
  1. Address correspondence and reprint requests to: Christopher J. Poole, MD, CR UK Clinical Trials Unit, University of Birmingham, Birmingham, B15 2TT, UK. Email: c.j.poole{at}bham.ac.uk

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/m2), and paclitaxel (starting 135 mg/m2) 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/m2 and paclitaxel 175 mg/m2. Reducing paclitaxel to 150 mg/m2 allowed escalation of gemcitabine to 1250 mg/m2, but neutropenia-related treatment delays occurred. Giving paclitaxel on day 1 (group C) enabled administration of paclitaxel 175 mg/m2 and gemcitabine 1250 mg/m2 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/m2 (day 1) and gemcitabine 1250 mg/m2 (days 1 and 8), with sequence of T→G, appears most suitable with tolerable toxicity and promising activity.

  • drug sequence
  • gemcitabine
  • MTD
  • paclitaxel
  • phase I
  • recurrent ovarian cancer
  • schedule

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Footnotes

  • This study was sponsored by Eli Lilly and Company.

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