Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab, capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer

Ann Oncol. 2013 Jul;24(7):1762-1769. doi: 10.1093/annonc/mdt124. Epub 2013 Mar 22.

Abstract

Background: To evaluate the efficacy and tolerability of preoperative short-course radiotherapy followed by capecitabine and oxaliplatin treatment in combination with bevacizumab and subsequent radical surgical treatment of all tumor sites in patients with stage IV rectal cancer.

Patients and methods: Adults with primary metastasized rectal cancer were enrolled. They received radiotherapy (5 × 5 Gy) followed by bevacizumab (7.5 mg/kg, day 1) and oxaliplatin (130 mg/m(2), day 1) intravenously and capecitabine (1000 mg/m(2) twice daily orally, days 1-14) for up to six cycles. Surgery was carried out 6-8 weeks after the last bevacizumab dose. The percentage of radical surgical treatment, 2-year survival and recurrence rates, and treatment-related toxicity was evaluated.

Results: Of 50 included patients, 42 (84%) had liver metastases, 5 (10%) lung metastases, and 3 (6%) both liver and lung metastases. Radical surgical treatment was possible in 36 (72%) patients. The 2-year overall survival rate was 80% [95% confidence interval (CI) 66.3%-90.0%]. The 2-year recurrence rate was 64% (95% CI 49.8%-84.5%). Toxic effects were tolerable. No treatment-related deaths occurred.

Conclusions: Radical surgical treatment of all tumor sites carried out after short-course radiotherapy, and bevacizumab-capecitabine-oxaliplatin combination therapy is a feasible and potentially curative approach in primary metastasized rectal cancer.

Keywords: bevacizumab; neoadjuvant chemotherapy; preoperative radiotherapy; rectal cancer; stage IV.

Publication types

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

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Capecitabine
  • Chemotherapy, Adjuvant
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Dose Fractionation, Radiation
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary
  • Liver Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local / prevention & control
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Radiotherapy, Adjuvant
  • Rectal Neoplasms / mortality
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / therapy*
  • Rectum / surgery*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Bevacizumab
  • Capecitabine
  • Fluorouracil