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Investigational New Drugs

, Volume 30, Issue 4, pp 1531–1539 | Cite as

Phase I study of axitinib (AG-013736) in combination with gemcitabine in patients with advanced pancreatic cancer

  • Jean-Philippe SpanoEmail author
  • Malcolm J. Moore
  • Yazdi K. Pithavala
  • Alejandro D. Ricart
  • Sinil Kim
  • Olivier Rixe
PHASE I STUDIES

Summary

Purpose Axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3, is under investigation for treatment of various solid tumors. The safety and pharmacokinetics of axitinib in combination with gemcitabine in patients with advanced pancreatic cancer was evaluated in the phase I portion of this trial. The randomized phase II portion was reported separately. Patients and methods Patients with advanced pancreatic cancer who had received no prior chemotherapy were eligible for this study. Pharmacokinetic profiles of the drugs were obtained on cycle (C) 1 day (D) 1 (gemcitabine alone 1,000 mg/m2), C1D14 (steady state, axitinib alone 5 mg twice daily [BID]), and C1D15 (gemcitabine plus steady-state axitinib). Adverse events were monitored weekly at the clinic. Results Eight patients participated in the phase IB portion of the trial. Patients received gemcitabine on D1, D8, and D15 and continuous axitinib in a 28 day-cycle beginning C1D3. There was no dose-limiting toxicity. Common treatment-related adverse events included fatigue, diarrhea, dysphonia, and hypertension. Myelosuppression was similar to gemcitabine monotherapy. No apparent major pharmacokinetic interactions between gemcitabine and axitinib were observed. Of six patients evaluable for efficacy, three had confirmed partial responses. Conclusions Axitinib (5 mg BID) and gemcitabine (1,000 mg/m2) were well tolerated when administered together, without any pharmacokinetic interactions, and showed encouraging antitumor activity.

Keywords

Axitinib Gemcitabine Combination Pharmacokinetics Pancreatic cancer 

Notes

Acknowledgements

The authors thank Prof. Laurent Hannoun, Hôpital de la Pitié Salpêtrière, Paris, France, for his critical contributions to the care of the patients enrolled in this study. Under guidance of authors, medical writing assistance was provided by Mukund Nori, PhD, MBA, CMPP at UBC Scientific Solutions and funded by Pfizer Inc. The authors thank Gamal ElSawah, MD, Pfizer Medical Affairs for his review of the manuscript. This study was sponsored by Pfizer Inc.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Jean-Philippe Spano
    • 1
    Email author
  • Malcolm J. Moore
    • 2
  • Yazdi K. Pithavala
    • 3
  • Alejandro D. Ricart
    • 4
  • Sinil Kim
    • 4
  • Olivier Rixe
    • 1
    • 5
  1. 1.Groupe Hospitalier Pitié-SalpêtrièreParis Cedex 13France
  2. 2.Princess Margaret HospitalTorontoCanada
  3. 3.Clinical Pharmacology Pfizer IncLa JollaUSA
  4. 4.Oncology Development Pfizer IncLa JollaUSA
  5. 5.Department of Hematology-OncologyUniversity of CincinnatiCincinnatiUSA

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