Investigational New Drugs

, Volume 28, Issue 4, pp 523–528

Phase II trial of sunitinib in patients with relapsed or refractory germ cell tumors

  • Darren R. Feldman
  • Stefan Turkula
  • Michelle S. Ginsberg
  • Nicole Ishill
  • Sujata Patil
  • Maryann Carousso
  • George J. Bosl
  • Robert J. Motzer
PHASE II STUDIES

DOI: 10.1007/s10637-009-9280-2

Cite this article as:
Feldman, D.R., Turkula, S., Ginsberg, M.S. et al. Invest New Drugs (2010) 28: 523. doi:10.1007/s10637-009-9280-2
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Summary

Vascular endothelial growth factor (VEGF) overexpression and increased angiogenesis have been proposed as having biologic importance in germ cell tumors (GCT). We conducted a single-institution phase II trial of sunitinib, an oral inhibitor of the VEGF receptor, in patients with relapsed or refractory GCT. A Simon’s two-stage design was used to determine the number of patients for enrollment. Responses were assessed using a modified version of Response Evaluation Criteria in Solid Tumors (RECIST), taking into account tumor marker changes. Dose modifications were made according to a nomogram for adverse events. Ten patients were enrolled. The first five received sunitinib 50 mg for four consecutive weeks, followed by a two-week break (4/2). Since four of five treated on this schedule had some tumor marker decline during the four-week “on” period, with subsequent rise during the two-week break, the dose was changed to 37.5 mg continuously for patients six to ten. However, only marker stabilization (no declines) was seen. Overall, there were no objective responses: Five had stable disease and five progressive disease (PD). Sunitinib was well tolerated; only one patient required a dose reduction due to grade 3 mucositis. Two patients experienced tumor-related hemorrhage (grade 3 and grade 1). All patients developed PD within three cycles. Sunitinib is well tolerated, but at standard doses, does not demonstrate significant activity in highly refractory GCT. Correlation between sunitinib treatment and tumor marker changes on the 50 mg 4/2 schedule suggest some pathways targeted by sunitinib (ie, angiogenesis) may be important to GCT biology.

Keywords

SunitinibGerm cell tumorsClinical trialPhase II

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Darren R. Feldman
    • 1
  • Stefan Turkula
    • 1
  • Michelle S. Ginsberg
    • 2
  • Nicole Ishill
    • 3
  • Sujata Patil
    • 3
  • Maryann Carousso
    • 1
  • George J. Bosl
    • 1
  • Robert J. Motzer
    • 1
  1. 1.Genitourinary Oncology Service, Department of MedicineMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department of RadiologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Department of Biostatistics, Epidemiology and StatisticsMemorial Sloan-Kettering Cancer CenterNew YorkUSA