Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Journal of Gastrointestinal Cancer
Published in: Journal of Gastrointestinal Cancer 1/2016

01-03-2016 | Original Research

Bevacizumab in Combination with Chemotherapy for Colorectal Brain Metastasis

Authors: Fabian Finkelmeier, Se-Jong You, Oliver Waidmann, Robert Wolff, Stefan Zeuzem, Oliver Bähr, Jörg Trojan

Published in: Journal of Gastrointestinal Cancer | Issue 1/2016

Login to get access

Abstract

Background

Brain metastases are rare in patients with colorectal cancer, but the incidence is expected to rise due to prolonged survival resulting from more effective regimens including anti-EGF-receptor and anti-angiogenic antibodies. Because of the potential fear of intracranial hemorrhage, patients with colorectal brain metastases have been excluded from clinical trials involving bevacizumab or aflibercept.

Patients

Five patients with colorectal brain metastases treated with bevacizumab-containing chemotherapy regimen following either neurosurgery, radiosurgery, or whole-brain radiotherapy were identified between 2009 and 2014. The clinicopathological data and outcomes for these patients were reviewed.

Results

Mean time to disease progression concerning brain metastases was 14.8 months (range 5–25). Overall survival was 26.2 months (range 7–42 months) and overall survival since diagnosis of brain metastases was 20.6 month (7–42). Best response was a partial response in two and a stable disease in three patients. Treatment-related adverse events were mild hypertension (grade 1), diarrhea (grade 1), and fatigue (grade 1). No intracranial hemorrhage was observed.

Conclusion

Bevacizumab in combination with chemotherapy is a feasible option for palliative treatment of patients with colorectal brain metastasis with a good safety profile.
Appendix
Available only for authorised users
Literature
1.
Ferlay J, Shin HR, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2008;127(12):2893–917.CrossRef
2.
Van der Pool AE, Damhuis RA, et al. Trends in incidence, treatment and survival of patients with stage IV colorectal cancer: a population based series. Color Dis. 2012;14(1):56–61.CrossRef
3.
Kopetz S, Chang GJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009;27(22):3677–83.PubMedCentralCrossRefPubMed
4.
Heinemann V, Fischer von Weikersthal L, Decker T, et al. Randomized comparison of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment of KRAS wild-type metastatic colorectal cancer: German AIO study KRK-0306 (FIRE-3). J Clin Oncol. 2013;31:2013 (suppl; abstr LBA3506).
5.
Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, et al. Open label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy refractory metastatic colorectal cancer. J Clin Oncol. 2007;25(13):1658–64.CrossRefPubMed
6.
Van Cutsem E, Tabernero J, Lakomy R, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol. 2012;30:3499–506.CrossRefPubMed
7.
8.
Schouten LJ, Rutten J, Huveneers HA, et al. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002;94:2698–705.CrossRefPubMed
9.
Jung M, Ahn JB, Chang JH, Suh CO, Hong S, et al. Brain metastases from colorectal carcinoma: prognostic factors and outcome. J Neuro-Oncol. 2011;101(1):49–55.CrossRef
10.
Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997;18:4–25.CrossRefPubMed
11.
Gerber HP, Dixit V, Ferrara N, et al. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J Biol Chem. 1998;273:13313–6.CrossRefPubMed
12.
Dvorak HF, Brown LF, Detmar M, Dvorak AM, et al. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146:1029–39.PubMedCentralPubMed
13.
Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983;219:983–5.CrossRefPubMed
14.
15.
Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. NEJM. 2004;350:2335–42.CrossRefPubMed
16.
Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer A, Figer R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26(12):2013–9.CrossRefPubMed
17.
Giantano BJ, Catalano PJ, Meropol NJ, O’Dwyer PJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer, results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007;25(12):1539–44.CrossRef
18.
Bennouna J, Sastre J, Arnold D, Österlund P, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013;14(1):29–37.CrossRefPubMed
19.
Gordon MS, Margolin K, Talpaz M, et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol. 2001;19:843–50.PubMed
20.
Sandler A, Gray R, Perry MC, et al. Paclitaxel–carboplatin alone or with bevacizumab for non–small-cell lung cancer. NEJM. 2006;355:2542–50.CrossRefPubMed
21.
Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370:2103–11.CrossRefPubMed
22.
Socinski MA, Langer CJ, Huang JE, et al. Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. J Clin Oncol. 2009;27:5255–61.CrossRefPubMed
23.
Archer V, Reck M, Sandler AB, et al. Risk of symptomatic central nervous system (CNS) progression and secondary hemorrhage in patients with non-squamous non-small cell lung cancer (NSCLC) receiving bevacizumab (BV)-based first-line therapy. J Clin Oncol. 2008;26:15. abstr 8114.
24.
Therasse P, Arbuck SG, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 2000;92(3):205–16.CrossRefPubMed
25.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRefPubMed
26.
Besse B, Lasserre SF, Compton P, Huang J, Augustus S, Rohr UP, et al. Bevacizumab safety in patients with central nervous system metastases. Clin Cancer Res. 2010;16(1):269–78.CrossRefPubMed
27.
Crinò L, Dansin E, Garrido P, et al. Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study. Lancet. 2010;11:733–40.CrossRefPubMed
28.
29.
Besse B, Le Moulec S, Senellart H, et al. Final overall survival (OS) results of a non comparative phase II study of bevacizumab (B) plus first-line chemotherapy or second-line erlotinib (E) in nonsquamous NSCLC patients with asymptomatic untreated brain metastases (BM)(BRAIN). J Clin Oncol. 2013; 31, (suppl; abstr 8059); ASCO Anual Meeting 2013; Abstract Number: 8059.
30.
Go PH, Klaassen Z, Meadows MC, Chamberlain R, et al. Gastrointestinal cancer and brain metastasis—a rare and omnious sign. Cancer. 2011;117(16):3630–40.CrossRefPubMed
31.
Cascino TL, Leavengood JM, Kemeny N, Posner JB. Brain metastases from colon cancer. J Neuro-Oncol. 1983;1:203–9.CrossRef
32.
Wronski M, Arbit E. Resection of brain metastases from colorectal carcinoma in 73 patients. Cancer. 1998;85:1677–85.CrossRef
33.
Bartelt S, Momm F, Weissenberger C, Lutterbach J, et al. Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy: prognostic factors and survival. World J Gastroenterol. 2004;10:3345–8.PubMedCentralCrossRefPubMed
34.
Farnell GF, Buckner JC, Cascino TL, O’Connell MJ, et al. Brain metastases from colorectal carcinoma. The long term survivors. Cancer. 1996;78:711–6.CrossRefPubMed
35.
Hammoud MA, McCutcheon IE, Elsouki R, Schoppa D, et al. Colorectal carcinoma and brain metastasis: distribution, treatment, and survival. Ann Surg Oncol. 1996;3:453–63.CrossRefPubMed
36.
Suzuki Y, Yamaguchi T, Matsumoto H, Nakano D, et al. Prognostic factors and treatment effects in patients with curatively resected brain metastasis from colorectal cancer. Dis Colon Rectum. 2014;57(1):56–63.CrossRefPubMed
37.
Tsao MN, Lloyd N, Wong RK, Chow E, Rakovitch E, Laperriere N. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev. 2012; 4:CD003869. doi:10.​1002/​14651858.​CD003869.​pub3.
38.
Patil CG, Pricola K, Sarmiento JM, Garg SK, Bryant A, Black Kl, et al. Whole brain radiation therapy (WBRt) alone versus WBRt and radiosurgery for the treatment of brain metastases. Cochrane Database Syst Rev. 2012; 9.
39.
O’Neill BP, Iturria NJ, Link MJ, Pollock BE, Ballman KV, O’Fallon JR, et al. A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases. Int J Radiat Oncol Biol Phys. 2003;55:1169–76.CrossRefPubMed
40.
Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC, et al. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys. 1999;45:427–34.CrossRefPubMed
41.
Poulsen NHS, Grunnet K, Sorensen M, Olsen P, et al. Bevacizumab plus irinotecan in the treatment patients with progressive recurrent malignant brain tumours. Acta Oncol. 2009;48:52–8.CrossRefPubMed
42.
Vredenburg JJ, Desjardins A, Hernon JE, Dowell JM, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007;13:1253–9.CrossRef
43.
Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27(28):4733–40.CrossRefPubMed
44.
Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. NEJM. 2014;370(8):699–708.PubMedCentralCrossRefPubMed
45.
Chinot OL, Wick W, Mason W, Henriksson R, Saran F, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. NEJM. 2014;370(8):709–22.CrossRefPubMed
46.
Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 2009;15:220–31.PubMedCentralCrossRefPubMed
Metadata
Title
Bevacizumab in Combination with Chemotherapy for Colorectal Brain Metastasis
Authors
Fabian Finkelmeier
Se-Jong You
Oliver Waidmann
Robert Wolff
Stefan Zeuzem
Oliver Bähr
Jörg Trojan
Publication date
01-03-2016
Publisher
Springer US
Published in
Journal of Gastrointestinal Cancer / Issue 1/2016
Print ISSN: 1941-6628
Electronic ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-015-9795-z

Other articles of this Issue 1/2016

Journal of Gastrointestinal Cancer 1/2016 Go to the issue

Original Research

Downregulated Expression of E-cadherin and TP53 in Patients with Gastric Diseases: the Involvement of H. pylori Infection and Its Virulence Markers

Original Research

The Detection of Cholangiocarcinoma in Primary Sclerosing Cholangitis Patients: Single Center Experience

Original Research

Epidemiological Study of Gallbladder Cancer Patients from North Indian Gangetic Planes—a High-Volume Centre’s Experience

Case Report

A Fulminant Case of Leptomeningeal Carcinomatosis Secondary to Esophageal Adenocarcinoma

Case Report

Anorectal Melanoma with Bilateral Ovarian Metastases

Letter to the Editor

The Multidisciplinary Management of Cancer in Daily Clinical Practice: Towards a Community Hospital Comprehensive Cancer Center
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits