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Investigational New Drugs

, Volume 31, Issue 5, pp 1244–1250 | Cite as

A Phase I Study of the combination of oxaliplatin/docetaxel and vandetanib for the treatment of advanced gastroesophageal cancer

  • Balazs Halmos
  • Yuxia Jia
  • Joseph A. Bokar
  • Pingfu Fu
  • David J. Adelstein
  • Rosalyn Juergens
  • Mary Beth Rodal
  • Afshin Dowlati
PHASE I STUDIES

Summary

Introduction This study aimed to assess the safety and tolerability of the multitargeted tyrosine kinase inhibitor, vandetanib (V), in combination with two chemotherapeutic agents, oxaliplatin (O) and docetaxel (D) in advanced gastroesophageal (GE) cancer. Methods This was a Phase I study (NCT00732745) with a standard 3 + 3 dose escalation design. The primary aim was to determine the optimal dose of the combination of vandetanib and OD chemotherapy. Results Initial treatment for the first cohort consisted of oxaliplatin at 100 mg/m2 on day 1, docetaxel at 35 mg/m2 on days 1 and 8 and vandetanib 100 mg PO daily of 21-day treatment cycles. As dose limiting toxicity (DLT) was reached in 2 out of 3 patients in cohort 1 (one grade 3 and one grade 4 diarrhea with dehydration), 6 patients were treated then at dose level −1 (O 80 mg/m2 on day 1, D 30 mg/m2 on days 1 and 8, V 100 mg PO daily days 1–21) in which no further DLTs were observed. This dose was established as maximum tolerated dose and is the recommended phase 2 dose. 8 out of 9 enrolled patients had adenocarcinoma. At dose level 1, 1 of the 3 patients had a documented partial response and 2 patients had stable disease. At dose level −1, 1 of 6 patients achieved a complete response, 2 of 6 patients had stable disease, and 3 of 6 patients had progressive disease. Conclusions Vandetanib added to oxaliplatin and docetaxel showed manageable toxicity and limited activity in advanced GE cancer.

Keywords

Vandetanib Oxaliplatin Docetaxel Phase I Gastroesophageal cancer 

Notes

Acknowledgments

The authors would like to express their gratitude to the nursing and support staff of University Hospitals of Cleveland/Case Comprehensive Cancer Center. This study was supported partially by Sanofi-Aventis and vandetanib was provided by Astra-Zeneca.

Ethical standards

The experiments comply with the current law of the US.

Conflict of interests

Dr. David J. Adelstein received research funding for the support of clinical studies from both Astra-Zeneca and Sanofi-Aventis and Balazs Halmos from Sanofi-Aventis while this study was being conducted.

The authors, Yuxia Jia, Joseph A. Bokar, Pingfu Fu, Rosalyn Juergens, Mary Beth Rodal, Afshin Dowlati, declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Balazs Halmos
    • 1
    • 2
  • Yuxia Jia
    • 2
  • Joseph A. Bokar
    • 1
  • Pingfu Fu
    • 1
  • David J. Adelstein
    • 3
  • Rosalyn Juergens
    • 4
  • Mary Beth Rodal
    • 1
  • Afshin Dowlati
    • 1
  1. 1.University Hospitals, Seidman Cancer CenterCase Western Reserve University, Case Comprehensive Cancer CenterClevelandUSA
  2. 2.Hematology/Oncology, New York Presbyterian HospitalColumbia University Medical CenterNew YorkUSA
  3. 3.Cleveland ClinicClevelandUSA
  4. 4.Johns Hopkins UniversityBaltimoreUSA

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