Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors: the xelbevoct study
1 Oncologia Medica, Dipartimento di Specialità Medico-Chirurgiche, Scienze Radiologiche e Sanità Pubblica, Università degli Studi di Brescia, Azienda Ospedaliera Spedali Civili Piazzale Spedali Civili 1, 25123 Brescia, Italy
2 Istituto Europeo di Oncologia IEO, NET study group, Via Ripamonti 435, 20141 Milan, Italy
3 Oncologia Medica, Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, AOU, San Luigi, Regione Gonzole, 10, 10043 Orbassano, TO, Italy
4 Anatomia Patologica, Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, AOU, San Luigi, Regione Gonzole, 10, 10043 Orbassano, TO, Italy
5 Dipartimento “Seràgnoli” di Scienze Ematologiche ed Oncologiche, Università di Bologna, Ospedale Sant’Orsola-Malpighi, Via G. Massarenti 9, 40138 Bologna, Italy
6 Oncologia Medica, I.R.C.C.S. Ospedale Casa Sollievo della Sofferenza, Viale Cappuccini 3, 71013 San Giovanni Rotondo, FG, Italy
7 Laboratorio di Farmacologia Clinica e Farmacogenetica, Dipartimento di Malattie Infettive, Università di Torino, Ospedale Amedeo di Savoia, C.so Svizzera 164, 10149 Torino, Italy
8 Radiologia, Dipartimento di Radiologia Diagnostica e Interventistica, Università di Torino, A.O.U. San Luigi, Regione Gonzole, 10, 10043 Orbassano, TO, Italy
9 Centro Oncologico Ematologico Subalpino COES, Azienda Ospedaliera Molinette, C.so Bramante 88, 10126 Torino, Italy
BMC Cancer 2014, 14:184 doi:10.1186/1471-2407-14-184Published: 14 March 2014
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.
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.
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.
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 number NCT01203306.