Bevacizumab in Combination with FOLFIRI in the First-Line Treatment of Patients with Advanced Colorectal Cancer: A Single-Institution Experience

Authors

  • Abigail Ruiz de Lobera Department of Medical Oncology, Hospital Universitario de Cruces, Plaza de Cruces s/n. 48903, Barakaldo, Spain
  • Aitziber Buqué Biological Research Unit, Hospital Universitario de Cruces, Plaza de Cruces s/n. 48903, Barakaldo, Spain
  • Alberto Muñoz Department of Medical Oncology, Hospital Universitario de Cruces, Plaza de Cruces s/n. 48903, Barakaldo, Spain
  • Sergio Carrera Department of Medical Oncology, Hospital Universitario de Cruces, Plaza de Cruces s/n. 48903, Barakaldo, Spain
  • Aintzane Sancho Department of Medical Oncology, Hospital Universitario de Cruces, Plaza de Cruces s/n. 48903, Barakaldo, Spain
  • Itziar Rubio Department of Medical Oncology, Hospital Universitario de Cruces, Plaza de Cruces s/n. 48903, Barakaldo, Spain
  • Eddy I. Gutierrez Department of Medical Oncology, Hospital Universitario de Cruces, Plaza de Cruces s/n. 48903, Barakaldo, Spain
  • Mikel Arruti Department of Medical Oncology, Hospital Universitario de Cruces, Plaza de Cruces s/n. 48903, Barakaldo, Spain
  • Inés Marrodán Department of Medical Oncology, Hospital Universitario de Cruces, Plaza de Cruces s/n. 48903, Barakaldo, Spain
  • Guillermo López-Vivanco Department of Medical Oncology, Hospital Universitario de Cruces, Plaza de Cruces s/n. 48903, Barakaldo, Spain

DOI:

https://doi.org/10.6000/1927-7229.2014.03.01.4

Keywords:

Bevacizumab, colorectal cancer, FOLFIRI, anticoagulant therapy, surgical rescue.

Abstract

 Introduction: Bevacizumab combined with IFL (irinotecan, bolus 5-fluorouracil, and leucovorin) has been shown to improve outcomes for patients with metastatic colorectal cancer (mCRC). However, infusional 5-fluorouracil-based combinations are now considered optimal in this setting. We analyzed the efficacy and toxicity of FOLFIRI (irinotecan, infusional 5-fluorouracil, and leucovorin)-bevacizumab in an unselected cohort of consecutive patients with mCRC.

Materials and Methods: Patients with unresectable mCRC received bevacizumab 5 mg/kg and irinotecan 180 mg/m² on day 1, leucovorin 200 mg/m² on days 1 and 2, 5-fluorouracil 400 mg/m² bolus, and 600 mg/m² continuous infusion on days 1 and 2, every 14 days. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were assessed.

Results: Overall, 127 patients were included (69% male, median age 64 years); 15 patients had diabetes, 40 had hypertension, and 23 were undergoing anticoagulant/antiplatelet therapy. Median PFS was 11.0 months (95% CI 10.0-12.0); median OS was 26.0 months (95% CI 21.9-30.1). The ORR was 55.1% (95% CI 46.3-63.6%), with 12 complete responses, 58 partial responses, and 44 patients with stable disease. Salvage surgery was performed in 31 patients (24%), including 23 with liver metastases and one with lung metastases. Grade 3/4 toxicities included neutropenia (17%), vomiting (6%), and diarrhea (17%); grade 3/4 bevacizumab-related toxicities included hypertension (2%), hemorrhage (2%), and venous (7%) and arterial thromboembolic events (5%).

Conclusion: FOLFIRI-bevacizumab was active and tolerable in this cohort of unselected patients with mCRC, resulting in a high surgical rescue rate and prolonged survival.

References

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90. http://dx.doi.org/10.3322/caac.20107

Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 2010; 46: 765-81. http://dx.doi.org/10.1016/j.ejca.2009.12.014

Surveillance, Epidemiology and End Results (SEER). SEER Stat Fact Sheets Colon and Rectum. http://seer.cancer. gov/statfacts/html/colorect.html#survival. Accessed 12 February 2013.

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335-42. http://dx.doi.org/10.1056/NEJMoa032691

Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol 2007; 25: 4779-86. http://dx.doi.org/10.1200/JCO.2007.11.3357

Sobrero A, Ackland S, Clarke S, Perez-Carrión R, Chiara S, Gapski J, et al. Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. Oncology 2009; 77: 113-9. http://dx.doi.org/10.1159/000229787

Van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, DiBartolomeo M, et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 2009; 20: 1842-7. http://dx.doi.org/10.1093/annonc/mdp233

Kozloff M, Yood MU, Berlin J, Flynn PJ, Kabbinavar FF, Purdie DM, et al. Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist 2009; 14: 862-70. http://dx.doi.org/10.1634/theoncologist.2009-0071

Bennouna J, Sastre J, Arnold D, Österlund P, Greil R, Van Cutsem E, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 2013; 14: 29-37. http://dx.doi.org/10.1016/S1470-2045(12)70477-1

Okines A, Puerto OD, Cunningham D, Chau I, Van Cutsem E, Saltz L, et al. Surgery with curative-intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer First BEAT and the randomised phase-III NO16966 trial. Br J Cancer 2009; 101: 1033-8. http://dx.doi.org/10.1038/sj.bjc.6605259

Van Cutsem E, Rivera F, Berry SR, Kretzschmar A, Michael M, DiBartolomeo M, et al. Exposure to anticoagulant medication in patients treated with bevacizumab: Subgroup analysis from the Bevacizumab Expanded Access Trial (BEAT). American Society of Clinical Oncology Gastrointestinal Cancers Symposium 2010; Abstract 431.

Hambleton J, Novotny WF, Hurwitz H, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab does not increase bleeding in patients with metastatic colorectal cancer receiving concurrent anticoagulation. J Clin Oncol 2004; 22(14S): Abstract 3528.

Leighl NB, Bennouna J, Yi J, Moore N, Hambleton J, Hurwitz H. Bleeding events in bevacizumab-treated cancer patients who received full-dose anticoagulation and remained on study. Br J Cancer 2011; 104: 413-8. http://dx.doi.org/10.1038/sj.bjc.6606074

Flynn PJ, Sugrue MM, Feng S, Purdie DM, Grothey A, Sargent DJ, et al. Incidence of serious bleeding events (sBE) in patients (pts) with metastatic colorectal cancer (mCRC) receiving bevacizumab (BV) as part of a first-line regimen: Results from the BRiTE observational cohort study (OCS). J Clin Oncol 2008; 26(15S): Abstract 4104.

Downloads

Published

2014-01-15

How to Cite

Abigail Ruiz de Lobera, Aitziber Buqué, Alberto Muñoz, Sergio Carrera, Aintzane Sancho, Itziar Rubio, Eddy I. Gutierrez, Mikel Arruti, Inés Marrodán, & Guillermo López-Vivanco. (2014). Bevacizumab in Combination with FOLFIRI in the First-Line Treatment of Patients with Advanced Colorectal Cancer: A Single-Institution Experience. Journal of Analytical Oncology, 3(1),  26–32. https://doi.org/10.6000/1927-7229.2014.03.01.4

Issue

Section

Articles