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

BMC Cancer. 2014 Mar 14;14:184. doi: 10.1186/1471-2407-14-184.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Metronomic
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab
  • Capecitabine
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Female
  • Fluorouracil / analogs & derivatives
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / pathology
  • Octreotide / administration & dosage*
  • Octreotide / adverse effects
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Deoxycytidine
  • Bevacizumab
  • Capecitabine
  • Octreotide
  • Fluorouracil

Associated data

  • ClinicalTrials.gov/NCT01203306