Efficacy and safety of bevacizumab in elderly patients with metastatic colorectal cancer: results from the Czech population-based registry

BMC Gastroenterology

Ladislav Dusek³  Ondrej Majek³  Jindrich Finek⁴  Jana Prausova¹  Rostislav Vyzula⁵  Bohuslav Melichar⁷  Tomas Buchler⁶  Zbynek Bortlicek³  Jiri Tomasek⁵  Tomas Pavlik³  Lubomir Slavicek² 

[1] Department of Oncology, Motol Hospital and Charles University, Prague, Czech Republic;Department of Oncology, Hospital Jihlava, Jihlava, Czech Republic;Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic;Department of Oncology, University Hospital Pilsen, Pilsen, Czech Republic;Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic;Department of Oncology and First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic;Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic

关键词: Progression-free survival;    Overall survival;    Elderly patients;    Chemotherapy;    Anti-angiogenic therapy;   

Others  :  855658
DOI  :  10.1186/1471-230X-14-53

 received in 2013-12-12, accepted in 2014-03-19,  发布年份 2014

【 摘 要 】

Background

Patients aged 65 years and older represent the majority of patients with metastatic colorectal cancer (mCRC). However, this patient population is often underrepresented in clinical trials and probably undertreated in the clinical practice.

Methods

We have analysed the outcomes of 3,187 mCRC patients treated with first-line bevacizumab based on data from the Czech national registry of mCRC patients aiming to compare the treatment efficacy and safety according to the age categories.

Results

In total, 2,126 (66.7%), 932 (29.2%), and 129 (4.0%) patients were aged <65 years, 65 to 75 years, and 75+ years, respectively. Median progression-free survival (PFS) was 11.4, 11.3, and 11.8 months for patients aged <65 years, 65 to 75 years, and 75+ years, respectively (p = 0.94). Median overall survival (OS) was 26.9, 27.5, and 25.1 months for patients aged <65 years, 65 to 75 years, and 75+ years, respectively (p = 0.73). Using multivariable Cox model for both PFS and OS, the patient age was not significantly associated with either PFS or OS. No increase in bevacizumab-related toxicity was observed among the elderly mCRC patients with the exception of hypertension, which was observed in 71 (3.3%), 34 (3.6%), and 10 (7.8%) patients aged <65 years, 65 to 75 years, and 75+ years, respectively.

Conclusions

The results of the present study suggest similar outcome in terms of OS and PFS with bevacizumab-containing therapy in elderly mCRC patients fit for chemotherapy combined with targeted therapy compared to younger patients. Thus, chronological age should not be considered to represent a limitation in prescribing bevacizumab-containing therapy in mCRC patients.

【 授权许可】

   
2014 Slavicek et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide. IARC CancerBase No. 10. Lyon: International Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr webcite
• [2]Dušek L, Mužík J, Kubásek M, Koptíková J, Zaloudík J, Vyzula R: Epidemiology of malignant tumours in the Czech Republic. [http://www.svod.cz webcite]
• [3]Kopetz S, Chang GJ, Overman MJ, Eng C, Sargent DJ, Larson DW, Grothey A, Vauthey JN, Nagorney DM, McWilliams RR: Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol 2009, 27:3677-3683.
• [4]Peeters M, Price T: Biologic therapies in the metastatic colorectal cancer treatment continuum–applying current evidence to clinical practice. Cancer Treat Rev 2012, 38:397-406.
• [5]Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F: Bevacizumab plus irinotecan, fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 2004, 250:2335-2342.
• [6]Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S: Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival in patiens with metastatic colorectal cancer. J Clin Oncol 2005, 23:3706-3712.
• [7]Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Cassidy J: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2013–2019, 2008:26.
• [8]Kozloff M, Yood MU, Berlin J, Flynn PJ, Kabbinavar FF, Purdie DM, Ashby MA, Dong W, Sugrue MM, Grothey A, Investigators of the BRiTE study: Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist 2009, 14:862-870.
• [9]Van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, DiBartolomeo M, Mazier MA, Canon JL, Georgoulias V, Peeters M, Bridgewater J, Cunningham D; First BEAT investigators: Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 1842–1847, 2009:20.
• [10]Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS: Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 2061–2067, 1999:341.
• [11]Dusek L: Czech Cancer Care in Numbers 2008–2009. Prague: Grada Publishing; 2009.
• [12]Kabbinavar FF, Hurwitz HI, Yi J, Sarkar S, Rosen O: Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized clinical trials. J Clin Oncol 2009, 27:199-205.
• [13]Cassidy J, Saltz LB, Giantonio BJ, Kabbinavar FF, Hurwitz HI, Rohr UP: Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. J Cancer Res Clin Oncol 2010, 136:737-743.
• [14]Price TJ, Zannino D, Wilson K, Simes RJ, Cassidy J, Van Hazel GA, Robinson BA, Broad A, Ganju V, Ackland SP, Tebbutt NC: Bevacizumab is equally effective and no more toxic in elderly patients with advanced colorectal cancer: a subgroup analysis from the AGITG MAX trial: an international randomised controlled trial of Capecitabine, Bevacizumab and Mitomycin C. Ann Oncol 2012, 23:1531-1536.
• [15]Kozloff MF, Berlin J, Flynn PJ, Kabbinavar F, Ashby M, Dong W, Sing AP, Grothey A: Clinical outcomes in elderly patients with metastatic colorectal cancer receiving bevacizumab and chemotherapy: results from the BRiTE observational cohort study. Oncology 2010, 78:329-339.
• [16]Němeček R, Tomášek J, Hejduk K, Bortlíček Z: Klinický registr CORECT. Klin onkol 2012, 25:480-485.
• [17]Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, Rothenberg ML, Green E, Sargent DJ: Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol 2006, 24:4085-4091.
• [18]Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin DB, Jonker D, Osborne S, Andre N, Waterkamp D, Saunders MP, AVEX study investigators: Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013, 14:1077-1085.
• [19]Meyerhardt JA, Li L, Sanoff HK, Carpenter W, Schrag D: Effectiveness of bevacizumab with first-line combination chemotherapy for Medicare patients with stage IV colorectal cancer. J Clin Oncol 2012, 30:608-615.
• [20]Zhu X, Wu S, Dahut WL, Parikh CR: Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. Am J Kidney Dis 2007, 49:186-193.
• [21]Tsai HT, Marshall JL, Weiss SR, Huang CY, Warren JL, Freedman AN, Fu AZ, Sansbury LB, Potosky AL: Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study. Ann Oncol 2013, 24:1574-1579.
• [22]Aprile G, Ferrari L, Fontanella C, Puglisi F: Bevacizumab in older patients with advanced colorectal or breast cancer. Crit Rev Oncol/Hematol 2013, 87:41-54.
• [23]Kyriakou F, Kountourakis P, Papamichael D: Targeted agents: review of toxicity in the elderly metastatic colorectal cancer patients. Target Oncol 2011, 6:245-251.
• [24]Pavlík T, Májek O, Büchler T, Vyzula R, Petera J, Ryska M, Ryška A, Cibula D, Babjuk M, Abrahámová J, Vorlíček J, Mužík J, Dušek L: Trends in stage-specific population-based survival of cancer patients in the Czech Republic in the period 2000–2008. Cancer Epidemiol 2014, 38:28-34.
• [25]Brenner H, Gondos A, Arndt V: Recent major progress in long-term cancer patient survival disclosed by modeled period analysis. J Clin Oncol 2007, 25:3274-3280.
• [26]Allemani C, Rachet B, Weir HK, Richardson LC, Lepage C, Faivre J, Gatta G, Capocaccia R, Sant M, Baili P, Lombardo C, Aareleid T, Ardanaz E, Bielska-Lasota M, Bolick S, Cress R, Elferink M, Fulton JP, Galceran J, Gózdz S, Hakulinen T, Primic-Zakelj M, Rachtan J, Diba CS, Sánchez MJ, Schymura MJ, Shen T, Tagliabue G, Tumino R, Vercelli M, et al.: Colorectal cancer survival in the USA and Europe: a CONCORD high-resolution study. BMJ Openin press