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Investigational New Drugs

, Volume 27, Issue 4, pp 356–365 | Cite as

Pemetrexed combined with paclitaxel: a dose-finding study evaluating three schedules in solid tumors

  • Axel-R. HanauskeEmail author
  • Herlinde Dumez
  • Martine Piccart
  • Emine Yilmaz
  • Tobias Graefe
  • Thierry Gil
  • Lorinda Simms
  • Luna Musib
  • Ahmad Awada
PHASE I STUDIES

Summary

The objectives of this phase I study were to determine the maximum tolerated dose (MTD), recommended phase II dose (RD), antitumor activity, safety, and pharmacokinetics of pemetrexed–paclitaxel combination. Patients (N = 95) with advanced solid tumors were assigned to three schedules (21-day cycles [q21d]). Starting doses for each schedule of pemetrexed and paclitaxel, respectively, were: (S1) 400 and 135 mg/m2 on d1; (S2) 400 mg/m2 d1 and 40 mg/m2 d1 and d8; S3) 400 mg/m2 d8 and 30 mg/m2 d1 and d8. MTD was 500/135 mg/m2 (S1), 400/40 mg/m2 (S2), and 500/120 mg/m2 (S3). Most common dose limiting toxicities were febrile neutropenia, fatigue, and neuromotor toxicities. Most common toxicity was grade 3/4 lymphopenia. Four patients had partial response, 43 patients had stable disease. The RD determined was pemetrexed 500 mg/m2 (d8) and paclitaxel 90 mg/m2 (d1 and d8), q21d. The combination was well tolerated and showed efficacy in thyroid carcinoma and mesothelioma.

Keywords

Pemetrexed Paclitaxel Phase I Combination chemotherapy Vitamin supplementation 

Notes

Acknowledgements

The authors are thankful for clinical support from Dr. Allan van Oosterom and for expert administrative and managerial support from Mrs. S. Kriebel-Bargholz during the conducting of this trial. From Eli Lilly and Company, we thank Bente Frimodt-Moller and Romnee Clark for medical support and David Cross and Parag Garhyan for pharmacokinetic analysis. Primo Scientific Corporation provided scientific writing support for this manuscript.

Research support

The financial support was provided by Eli Lilly and Company.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Axel-R. Hanauske
    • 1
    Email author
  • Herlinde Dumez
    • 2
  • Martine Piccart
    • 3
  • Emine Yilmaz
    • 1
  • Tobias Graefe
    • 1
  • Thierry Gil
    • 3
  • Lorinda Simms
    • 5
  • Luna Musib
    • 4
  • Ahmad Awada
    • 3
  1. 1.St. Georg HospitalHamburgGermany
  2. 2.UZ GasthuisbergLeuvenBelgium
  3. 3.Institut Jules BordetUniversité Libre de BruxellesBrusselsBelgium
  4. 4.Eli Lilly and CompanyIndianapolisUSA
  5. 5.Eli Lilly and CompanyTorontoCanada

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