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Open Access Research article

Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors: the xelbevoct study

Alfredo Berruti1*, Nicola Fazio2, Anna Ferrero3, Maria Pia Brizzi3, Marco Volante4, Elisabetta Nobili5, Lucia Tozzi6, Lisa Bodei3, Mirella Torta3, Antonio D’Avolio7, Adriano Massimiliano Priola8, Nadia Birocco9, Vito Amoroso1, Guido Biasco5, Mauro Papotti4 and Luigi Dogliotti3

Author Affiliations

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

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BMC Cancer 2014, 14:184  doi:10.1186/1471-2407-14-184

Published: 14 March 2014

Abstract

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.

Keywords:
Bevacizumab; Pancreatic endocrine tumor; Capecitabine; Octreotide