Sandwich-like neoadjuvant therapy with bevacizumab for locally advanced rectal cancer: a phase II trial

Cancer Chemother Pharmacol. 2015 Jul;76(1):21-7. doi: 10.1007/s00280-015-2763-2. Epub 2015 May 8.

Abstract

Purpose: Current neoadjuvant chemoradiotherapy had limited impact on distal metastasis and survival in locally advanced rectal cancer. Here, we investigated a new sandwich-like neoadjuvant regimen with bevacizumab.

Methods: This was a single-arm, open-labeled, phase II trial. Patients with locally advanced rectal cancer received sandwich-like neoadjuvant therapy with bevacizumab (induction therapy with bevacizumab and FOLFOX, concurrent chemoradiotherapy with bevacizumab and consolidation chemotherapy with FOLFOX). Surgery was performed 4-6 weeks later. The primary endpoint of this study was pathologic complete response.

Results: Twenty-five eligible patients were included. All completed the neoadjuvant therapy protocol. During the course of neoadjuvant therapy, 3 patients (12 %) had grade 4 hematological toxicity events and 12 (48 %) had grade 3 non-hematological toxicity events. According to RECIST criteria, 18 patients (72 %) achieved partial response and the rest seven patients (28 %) remained stable disease. Two patients (8 %) refused the subsequent surgical therapy for personal reasons, and 23 patients (92 %) underwent operations finally. Nine (39.1 %, 95 % CI 18.0-57.5 %) of them achieved pathologic complete response. Five of them (21.7 %) had postoperative complications. After a median follow-up period of 25.3 (14.4-40.9) months, four patients developed disease progression and two died of cancer. The 3-year overall survival rate was 95 % (95 % CI 69.5-99.3 %), and the 3-year disease-free survival rate was 72.5 % (95 % CI 33.7-90.9 %).

Conclusions: Sandwich-like neoadjuvant therapy with bevacizumab is safe and effective for locally advanced rectal cancer.

Trial registration: ClinicalTrials.gov NCT01554059.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Chemoradiotherapy
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Organoplatinum Compounds / administration & dosage
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / radiotherapy
  • Rectal Neoplasms / surgery
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Organoplatinum Compounds
  • Bevacizumab
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol

Associated data

  • ClinicalTrials.gov/NCT01554059