A phase II clinical trial of sunitinib following hepatic transarterial embolization for metastatic neuroendocrine tumors.
BACKGROUND
The liver is the predominant site of metastases among patients with advanced neuroendocrine tumors (NETs). Prior retrospective studies have reported high response rates in patients treated with transarterial embolization (TAE). NETs are highly vascular and are known to express vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR). We hypothesized that administration of sunitinib, a VEGFR inhibitor, following TAE would extend progression-free survival (PFS).


METHODS
Patients with metastatic NETs to the liver underwent a series of selective TAEs followed by sunitinib (until disease progression or maximum of 12 months). Radiographic response (by RECIST), survival, and safety parameters were monitored.


RESULTS
Thirty-nine patients were enrolled. The overall response rate was 72% [95% confidence interval (CI), 0.58-0.86]. Median PFS was 15.2 months. Rates of overall survival (OS) at 1 and 4 years were 95% (95% CI, 0.88-1.00) and 59% (95% CI, 0.38-0.80), respectively. A significant 34% rise in serum VEGF was observed following the initial TAE (P = 0.03).


CONCLUSIONS
Hepatic TAE is a highly active treatment option for patients with metastatic NETs to the liver. Embolization stimulates release of VEGF into the circulation. Sunitinib, an oral VEGFR inhibitor, can be safely administered following embolization. The high rates of PFS and OS associated with this sequence of therapies are encouraging.
Departments of Gastrointestinal Oncology. Electronic address: jonathan.strosberg@moffitt.org.
J R
JR
Strosberg
Departments of Gastrointestinal Oncology.
J M
JM
Weber
Departments of Interventional Radiology.
J
J
Choi
Departments of Gastrointestinal Oncology.
T L
TL
Campos
Departments of Gastrointestinal Oncology.
T L
TL
Valone
Departments of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA.
G
G
Han
Departments of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA.
M J
MJ
Schell
Departments of Gastrointestinal Oncology.
L K
LK
Kvols
D000180:Acrylic Resins / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004621:Embolization, Therapeutic; D005260:Female; D005780:Gelatin / Q000627:therapeutic use; D006499:Hepatic Artery; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D007414:Intestinal Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018358:Neuroendocrine Tumors; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D000077210:Sunitinib; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D000180:Acrylic Resins; D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C496735:trisacryl gelatin microspheres; D005780:Gelatin; D000077210:Sunitinib