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


Authors: Feldman, D. R.; Turkula, S.; Ginsberg, M. S.; Ishill, N.; Patil, S.; Carousso, M.; Bosl, G. J.; Motzer, R. J.
Article Title: Phase II trial of sunitinib in patients with relapsed or refractory germ cell tumors
Abstract: 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 fourweek "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. © Springer Science + Business Media, LLC 2009.
Keywords: adult; clinical article; treatment outcome; middle aged; clinical trial; drug tolerability; fatigue; neutropenia; sunitinib; cancer growth; dose response; drug dose reduction; drug efficacy; hypertension; side effect; antineoplastic agents; antineoplastic agent; neoplasm; multiple cycle treatment; phase 2 clinical trial; anemia; leukopenia; mucosa inflammation; neuropathy; thrombocytopenia; drug administration schedule; tumor markers, biological; recurrence; drug effect; drug resistance; dose-response relationship, drug; drug resistance, neoplasm; tumor marker; hyperglycemia; lymphocytopenia; hypoalbuminemia; hyponatremia; blood; drug response; testis tumor; testicular neoplasms; recurrent disease; cancer relapse; hyperbilirubinemia; neoplasms, germ cell and embryonal; drug administration; indoles; pyrroles; indole derivative; germ cell tumor; mediastinum tumor; mediastinal neoplasms; germ cell tumors; phase ii; epistaxis; pyrrole derivative
Journal Title: Investigational New Drugs
Volume: 28
Issue: 4
ISSN: 0167-6997
Publisher: Springer  
Date Published: 2010-08-01
Start Page: 523
End Page: 528
Language: English
DOI: 10.1007/s10637-009-9280-2
PUBMED: 19547919
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: INNDD" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Sujata Patil
    386 Patil
  2. Robert Motzer
    769 Motzer
  3. Michelle S Ginsberg
    159 Ginsberg
  4. Darren Richard Feldman
    172 Feldman
  5. George Bosl
    270 Bosl
  6. Nicole Marie Leoce
    86 Leoce