TY - JOUR
T1 - Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors
T2 - The xelbevoct study
AU - Berruti, Alfredo
AU - Fazio, Nicola
AU - Ferrero, Anna
AU - Brizzi, Maria P.
AU - Volante, Marco
AU - Nobili, Elisabetta
AU - Tozzi, Lucia
AU - Bodei, Lisa
AU - Torta, Mirella
AU - D'Avolio, Antonio
AU - Priola, Adriano M.
AU - Birocco, Nadia
AU - Amoroso, Vito
AU - Biasco, Guido
AU - Papotti, Mauro
AU - Dogliotti, Luigi
PY - 2014/3/14
Y1 - 2014/3/14
N2 - Background: We assessed the activity and toxicity of the XELBEVOCT regimen in patients with metastatic well-to-moderately differentiated neuroendocrine neoplasms (WMD-NEN). Ancillary studies evaluated hypertension, proteinuria, and vascular endothelial growth factor (VEGF) polymorphisms in predicting progression-free survival (PFS) and the predictive role of serum vitamin D in progression-free survival and proteinuria onset.Methods: This prospective phase 2 study included 45 patients with WMD-NEN arising from various primary sites. The treatment regimen was octreotide long-acting release (LAR), 20 mg monthly, metronomic capecitabine, 2000 mg/daily, and intravenous bevacizumab, 5 mg/kg every 2 weeks, without interruption for 9 months. Bevacizumab was continued until disease progression.Results: Partial response was obtained in 8 patients (17.8%, 95% confidence interval [CI], 6.4%-28.2%); tumor response was more frequent in pancreatic than in non-pancreatic malignancies. The median PFS was 14.9 months; median overall survival was not attained. Biochemical and symptomatic responses were observed in 52.9% and 82.3% of cases, respectively. The treatment was well tolerated. Grade 3 toxicities included hand and foot syndrome (11.1%), proteinuria (4.4%), and renal toxicity (2.2%). Proteinuria (all grades) was correlated with longer PFS (p = 0.017). There was an inverse relationship between proteinuria and vitamin D levels. VEGF polymorphisms were not associated with patient outcome.Conclusion: The XELBEVOCT regimen is active and well tolerated in patients with metastatic WMD-NEN. Proteinuria correlated with hypovitaminosis D status and was the best predictive factor of treatment efficacy.Trial registration: Trial registration number NCT01203306.
AB - Background: We assessed the activity and toxicity of the XELBEVOCT regimen in patients with metastatic well-to-moderately differentiated neuroendocrine neoplasms (WMD-NEN). Ancillary studies evaluated hypertension, proteinuria, and vascular endothelial growth factor (VEGF) polymorphisms in predicting progression-free survival (PFS) and the predictive role of serum vitamin D in progression-free survival and proteinuria onset.Methods: This prospective phase 2 study included 45 patients with WMD-NEN arising from various primary sites. The treatment regimen was octreotide long-acting release (LAR), 20 mg monthly, metronomic capecitabine, 2000 mg/daily, and intravenous bevacizumab, 5 mg/kg every 2 weeks, without interruption for 9 months. Bevacizumab was continued until disease progression.Results: Partial response was obtained in 8 patients (17.8%, 95% confidence interval [CI], 6.4%-28.2%); tumor response was more frequent in pancreatic than in non-pancreatic malignancies. The median PFS was 14.9 months; median overall survival was not attained. Biochemical and symptomatic responses were observed in 52.9% and 82.3% of cases, respectively. The treatment was well tolerated. Grade 3 toxicities included hand and foot syndrome (11.1%), proteinuria (4.4%), and renal toxicity (2.2%). Proteinuria (all grades) was correlated with longer PFS (p = 0.017). There was an inverse relationship between proteinuria and vitamin D levels. VEGF polymorphisms were not associated with patient outcome.Conclusion: The XELBEVOCT regimen is active and well tolerated in patients with metastatic WMD-NEN. Proteinuria correlated with hypovitaminosis D status and was the best predictive factor of treatment efficacy.Trial registration: Trial registration number NCT01203306.
KW - Bevacizumab
KW - Capecitabine
KW - Octreotide
KW - Pancreatic endocrine tumor
UR - http://www.scopus.com/inward/record.url?scp=84899085315&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899085315&partnerID=8YFLogxK
U2 - 10.1186/1471-2407-14-184
DO - 10.1186/1471-2407-14-184
M3 - Article
C2 - 24628963
AN - SCOPUS:84899085315
VL - 14
JO - BMC Cancer
JF - BMC Cancer
SN - 1471-2407
IS - 1
M1 - 184
ER -