Investigational New Drugs

, Volume 37, Issue 4, pp 658–665 | Cite as

A phase I study of the vascular endothelial growth factor inhibitor Vatalanib in combination with Pemetrexed disodium in patients with advanced solid tumors

  • Fen Wang
  • Julian Molina
  • Daniel Satele
  • Jun Yin
  • Vun-Sin Lim
  • Alex A. AdjeiEmail author


Introduction Vatalanib is an oral receptor tyrosine kinase inhibitor that blocks all known VEGF, PDGF, and c-Kit receptors. This phase I study evaluated the safety, tolerability, and biologic activity of the combination of vatalanib with pemetrexed disodium in patients with advanced solid tumors. Methods Patients were administered escalating twice daily doses of vatalanib in combination with pemetrexed disodium in 21-day cycles. A dose expansion cohort was enrolled to further define the maximum tolerated dose (MTD) and further evaluate efficacy. Results A total of 29 patients were enrolled in the study (dose escalation, 9; dose expansion, 20). Dose-limiting toxicities included grade 4 thrombocytopenia (6.9%) and febrile neutropenia, anorexia, constipation, and dehydration. Other common adverse events were fatigue (75%), nausea (66%), vomiting (48%), oral mucositis (31%) and diarrhea (28%). The majority of these toxicities were Grade 1–2. The MTD was reached at vatalanib 250 mg twice daily continuously combined with pemetrexed disodium 500 mg/m2 day 1. Overall, 2 patients (6.9%) had partial responses, 8 (27.6%) had stable disease for at least 4 cycles, 5 had progressive disease (17.2%) and 5 went off study before disease assessment. Conclusion The combination of vatalanib with pemetrexed disodium was feasible, but not well tolerated. The modest efficacy results are consistent with other results obtained from combinations of chemotherapy and a large number of VEGF tyrosine kinase inhibitors. This combination should not be developed further unless predictive biomarkers can be identified.


Vatalanib Pemetrexed Phase I VEGF inhibitor Solid tumors 



This study was funded by the National Cancer Institute P30CA015083 grant.

Compliance with ethical standards

Conflict of interests

All authors have no conflict of interest to report.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Fen Wang
    • 1
  • Julian Molina
    • 2
  • Daniel Satele
    • 3
  • Jun Yin
    • 3
  • Vun-Sin Lim
    • 2
  • Alex A. Adjei
    • 2
    Email author
  1. 1.Department of OncologyPeking University Shenzhen HospitalShenzhenChina
  2. 2.Department of OncologyMayo ClinicRochesterUnited States
  3. 3.Department of Health Sciences ResearchMayo ClinicRochesterUnited States

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