Capecitabine in combination with oxaliplatin and bevacizumab (AXELOX) as 1st line treatment for fit and vulnerable elderly patients (aged >70 years) with metastatic colorectal cancer (mCRC): a multicenter phase II study of the Hellenic Oncology Research Group (HORG)

Lambros Vamvakas, Alexios Matikas, Athanasios Karampeazis, Dora Hatzidaki, Stelios Kakolyris, Charalampos Christophylakis, Ioannis Boukovinas, Aris Polyzos, Vassilis Georgoulias, John Souglakos, Lambros Vamvakas, Alexios Matikas, Athanasios Karampeazis, Dora Hatzidaki, Stelios Kakolyris, Charalampos Christophylakis, Ioannis Boukovinas, Aris Polyzos, Vassilis Georgoulias, John Souglakos

Abstract

Background: Colorectal cancer (CRC) is a disease of the elderly. However, geriatric patients are often excluded from clinical trials. The combination of capecitabine, oxaliplatin and bevacizumab (XELOX/BEV) has not been assessed in an elderly population.

Methods: We conducted a phase II study of XELOX plus bevacizumab combination as first line treatment in elderly patients with metastatic CRC. Treatment consisted of capecitabine 750 mg/m2 twice a day during days 1-7, oxaliplatin 85 mg/m2 and bevacizumab 5 mg/kg on day 1. Treatment was repeated every 14 days. The primary endpoint was overall response rate.

Results: In the 48 enrolled patients response rate according was 46.8% (95% CI: 32.54%-61.07%), while 13 patients had stable disease, for an overall disease control rate of 74.4% (95% CI: 57.8-91.2). Progression free survival was 7.9 months (95% CI: 5.9-9.8 months) and the median overall survival 20.1 months (95% CI: 15.6-25.7 months). Response rate and progression free survival has been correlated with baseline albumin and haemoglobin levels. There was one treatment-related death. Grade 3-4 toxicities were asthenia (4.2%), neurotoxicity (2.1%) and diarrhea 6.3%).

Conclusions: The combination of capecitabine, oxaliplatin and bevacizumab is an effective and safe combination for the treatment of elderly patients with metastatic CRC.

Trial registration: Clinical trials NCT01024504, 26 November 2010.

Figures

Figure 1
Figure 1
Progression free survival according to baseline albumin levels.
Figure 2
Figure 2
Progression free survival according to baseline haemoglobin levels.
Figure 3
Figure 3
Overall survival according to baseline haemoglobin levels.

References

    1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008;58(2):71–96. doi: 10.3322/CA.2007.0010.
    1. Edwards BK, Brown ML, Wingo PA, Howe HL, Ward E, Ries LA, Schrag D, Jamison PM, Jemal A, Wu XC, Friedman C, Harlan L, Warren J, Anderson RN, Pickle LW. Annual report to the nation on the status of cancer, 1975-2002, featuring population-based trends in cancer treatment. J Natl Cancer Inst. 2005;97(19):1407–1427. doi: 10.1093/jnci/dji289.
    1. Sawhney R, Sehl M, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part I. Cancer J. 2005;11(6):449–460. doi: 10.1097/00130404-200511000-00004.
    1. Sehl M, Sawhney R, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part II. Cancer J. 2005;11(6):461–473. doi: 10.1097/00130404-200511000-00005.
    1. Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, Lichtman SM, Gajra A, Bhatia S, Katheria V, Klapper S, Hansen K, Ramani R, Lachs M, Wong FL, Tew WP. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457–3465. doi: 10.1200/JCO.2011.34.7625.
    1. Soubeyran P, Fonck M, Blanc-Bisson C, Blanc JF, Ceccaldi J, Mertens C, Imbert Y, Cany L, Vogt L, Dauba J, Andriamampionona F, Houédé N, Floquet A, Chomy F, Brouste V, Ravaud A, Bellera C, Rainfray M. Predictors of early death risk in older patients treated with first-line chemotherapy for cancer. J Clin Oncol. 2012;30(15):1829–1834. doi: 10.1200/JCO.2011.35.7442.
    1. Stuck AE, Siu AL, Wieland GD, Adams J, Rubenstein LZ. Comprehensive geriatric assessment: a meta-analysis of controlled trials. Lancet. 1993;342(8878):1032–1036. doi: 10.1016/0140-6736(93)92884-V.
    1. 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(25):4085–4091. doi: 10.1200/JCO.2006.06.9039.
    1. Mattioli R, Massacesi C, Recchia F, Marcucci F, Cappelletti C, Imperatori L, Pilone A, Rocchi M, Cesta A, Laici G, Bonsignori M, Lippe P. High activity and reduced neurotoxicity of bi-fractionated oxaliplatin plus 5-fluorouracil/leucovorin for elderly patients with advanced colorectal cancer. Ann Oncol. 2005;16(7):1147–1151. doi: 10.1093/annonc/mdi222.
    1. Sastre J, Aranda E, Massuti B, Tabernero J, Chaves M, Abad A, Carrato A, Reina JJ, Queralt B, Gomez-Espana A, Gonzalez-Flores E, Rivera F, Losa F, Garcia T, Sanchez-Rovira P, Maestu I, Diaz-Rubio E. Elderly patients with advanced colorectal cancer derive similar benefit without excessive toxicity after first-line chemotherapy with oxaliplatin-based combinations: comparative outcomes from the 03-TTD-01 phase III study. Crit Rev Oncol Hematol. 2009;70(2):134–144. doi: 10.1016/j.critrevonc.2008.11.002.
    1. Seymour MT, Thompson LC, Wasan HS, Middleton G, Brewster AE, Shepherd SF, O’Mahony MS, Maughan TS, Parmar M, Langley RE. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet. 2011;377(9779):1749–1759. doi: 10.1016/S0140-6736(11)60399-1.
    1. 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. 2009;20(11):1842–1847. doi: 10.1093/annonc/mdp233.
    1. Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, Nordlinger B, van de Velde CJ, Balmana J, Regula J, Nagtegaal ID, Beets-Tan RG, Arnold D, Ciardiello F, Hoff P, Kerr D, Köhne CH, Labianca R, Price T, Scheithauer W, Sobrero A, Tabernero J, Aderka D, Barroso S, Bodoky G, Douillard JY, El Ghazaly H, Gallardo J, Garin A, Glynne-Jones R. et al.ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol. 2012;23(10):2479–2516. doi: 10.1093/annonc/mds236.
    1. 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(6):1574–1579. doi: 10.1093/annonc/mdt019.
    1. 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(11):1077–1085. doi: 10.1016/S1470-2045(13)70154-2.
    1. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205–216. doi: 10.1093/jnci/92.3.205.
    1. Basso U, Monfardini S. Multidimensional geriatric evaluation in elderly cancer patients: a practical approach. Eur J Cancer Care (Engl) 2004;13(5):424–433. doi: 10.1111/j.1365-2354.2004.00551.x.
    1. Kakolyris S, Souglakos J, Polyzos A, Ardavanis A, Ziras N, Athanasiadis A, Varthalitis I, Amarantidis K, Tsousis S, Vamvakas L, Vardakis N, Georgoulias V. Hellenic Oncology Research Group. Modified CAPOX (capecitabine plus oxaliplatin) regimen every two weeks as second-line treatment in patients with advanced colorectal cancer previously treated with irinotecan-based frontline therapy: a multicenter phase II study. Oncology. 2008;74(1–2):31–36.
    1. Aparicio T, Jouve JL, Teillet L, Gargot D, Subtil F, Le Brun-Ly V, Cretin J, Locher C, Bouche O, Breysacher G, Charneau J, Seitz JF, Gasmi M, Stefani L, Ramdani M, Lecomte T, Mitry E. Geriatric factors predict chemotherapy feasibility: ancillary results of FFCD 2001-02 phase III study in first-line chemotherapy for metastatic colorectal cancer in elderly patients. J Clin Oncol. 2013;31(11):1464–1470. doi: 10.1200/JCO.2012.42.9894.
    1. 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(5–6):329–339.
    1. 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(2):199–205. doi: 10.1200/JCO.2008.17.7931.
    1. 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(6):1531–1536. doi: 10.1093/annonc/mdr488.
    1. Venderbosch S, Doornebal J, Teerenstra S, Lemmens W, Punt CJ, Koopman M. Outcome of first line systemic treatment in elderly compared to younger patients with metastatic colorectal cancer: a retrospective analysis of the CAIRO and CAIRO2 studies of the Dutch Colorectal Cancer Group (DCCG) Acta Oncol. 2012;51(7):831–839. doi: 10.3109/0284186X.2012.699193.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi