Subscribe to RSS
DOI: 10.1055/a-1149-2282
Gastrointestinale Tumoren beim älteren und alten Patienten
Gastrointestinal tumors in older patientsZusammenfassung
Ältere Patienten (65 Jahre und älter) stellen die Mehrheit der Patienten mit einer Krebsdiagnose dar. Für Ösophaguskarzinome liegt der Altersgipfel in der siebten bis achten Lebensdekade. Bei Magenkarzinomen ist 1/3 der Patienten älter als 75 Jahre, und ca. 45 % der Kolonkarzinom-Patienten sind ≥ 75 Jahre alt.
Aufgrund bestehender Komorbiditäten, altersbedingter Veränderungen und Polypharmazie stellen ältere und alte Patienten eine besondere Herausforderung in der Tumortherapie dar.
In Studien sind diese Patienten meist deutlich unterrepräsentiert, und dezidierte „Elderly“-Studien sind rar. Neue Operationsverfahren mit der minimalinvasiven Technik wie der Laparoskopie oder mit Telemanipulatoren liefern gerade für das Ösophagus- und Magenkarzinom Vorteile, die zukünftig für alte und ältere Patienten die postoperative Morbidität in Bezug auf kardiale und pulmonale Komplikationen deutlich senken können.
Bezüglich Chemotherapie zeigt sich eine gute Verträglichkeit von Fluoropyrimidinen und Oxaliplatin; von Triple-Therapien sollte eher Abstand genommen werden. Gerade die Immuntherapie bietet aufgrund des besseren Nebenwirkungsprofils eine interessante Alternative zur Standardchemotherapie.
Abstract
Older patients (65 years and over) represent the majority of patients with a cancer diagnosis. For oesophageal carcinomas, the age peak is in the seventh to eighth decade of life. In gastric carcinoma, 1/3 of patients are older than 75 years and approximately 45 % of colon carcinoma patients are ≥ 75 years old.
Due to existing comorbidities, age-related changes and polypharmacy, older patients present a special challenge in tumor therapy.
In studies, these patients are usually clearly under-represented and „elderly“-studies are rare.
New surgical procedures with laparoscopy and also robotic provide advantages for esophageal and gastric carcinoma, which in the future can reduce postoperative morbidity in relation to cardiac and pulmonary complications for old and older patients. The selection of suitable patients is essential here.
With regard to chemotherapy, fluoropyrimidines and oxaliplatin are well tolerated; triplet therapies should be avoided. Immunotherapy in particular offers an interesting alternative to standard chemotherapy due to its better side effect profile.
Publication History
Received: 08 November 2019
Accepted: 26 March 2020
Article published online:
16 June 2020
© Georg Thieme Verlag KG
Stuttgart · New York
-
Literatur
- 1 Yancik R, Ries LA. Cancer in older persons: an international issue in an aging world. Semin Oncol 2004; 31: 128-136
- 2 Yee KW, Pater JL, Pho L. et al Enrollment of older patients in cancer treatment trials in Canada: why is age a barrier?. J Clin Oncol 2003; 21: 1618-1623 . doi:10.1200/jco.2003.12.044
- 3 Talarico L, Chen G, Pazdur R. Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol 2004; 22: 4626-4631 . doi:10.1200/jco.2004.02.175
- 4 Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist 2000; 5: 224-237 . doi:10.1634/theoncologist.5-3-224
- 5 Extermann M, Boler I, Reich RR. et al Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer 2012; 118: 3377-3386 . doi:10.1002/cncr.26646
- 6 Ferlay J, Colombet M, Soerjomataram I. et al Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer 2018; 103: 356-387 . doi:10.1016/j.ejca.2018.07.005
- 7 Gupta B, Kumar N. Worldwide incidence, mortality and time trends for cancer of the oesophagus. Eur J Cancer Prev 2017; 26: 107-118 . doi:10.1097/cej.0000000000000249
- 8 Singh S, Sharma AN, Murad MH. et al Central adiposity is associated with increased risk of esophageal inflammation, metaplasia, and adenocarcinoma: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2013; 11: 1399-1412 .e1397. doi:10.1016/j.cgh.2013.05.009
- 9 Pech O, May A, Manner H. et al Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus. Gastroenterology 2014; 146: 652-660.e651 . doi:10.1053/j.gastro.2013.11.006
- 10 Sgourakis G, Gockel I, Karaliotas C. et al Survival after chemotherapy and/or radiotherapy versus self-expanding metal stent insertion in the setting of inoperable esophageal cancer: a case-control study. BMC Cancer 2012; 12: 70 . doi:10.1186/1471-2407-12-70
- 11 Lai A, Lipka S, Kumar A. et al Role of Esophageal Metal Stents Placement and Combination Therapy in Inoperable Esophageal Carcinoma: A Systematic Review and Meta-analysis. Dig Dis Sci 2018; 63: 1025-1034 . doi:10.1007/s10620-018-4957-z
- 12 Soubeyran P, Fonck M, Blanc-Bisson C. et al Predictors of early death risk in older patients treated with first-line chemotherapy for cancer. J Clin Oncol 2012; 30: 1829-1834 . doi:10.1200/jco.2011.35.7442
- 13 Conti S, West JP, Fitzpatrick HF. Mortality and morbidity after esophagogastrectomy for cancer of the esophagus and cardia. Am Surg 1977; 43: 92-96
- 14 Clavier JB, Antoni D, Atlani D. et al Baseline nutritional status is prognostic factor after definitive radiochemotherapy for esophageal cancer. Dis Esophagus 2014; 27: 560-567 . doi:10.1111/j.1442-2050.2012.01441.x
- 15 Oakley B, Lamb C, Vohra R. et al Achieving long term survival in oesophagectomy patients aged over 75. Ann Med Surg (Lond) 2016; 9: 15-21 . doi:10.1016/j.amsu.2016.05.016
- 16 Molenaar CJL P-BN, Herrle F, Slooter GD. Prehabilitation, making patients fit for surgery – a new frontier in perioperative care. DOI: https://doi.org/10.1515/iss-2019-0017.
- 17 Triantafyllou T, Olson MT, Theodorou D. et al. Enhanced recovery pathways vs standard care pathways in esophageal cancer surgery: systematic review and meta-analysis. Esophagus 2020; DOI: 10.1007/s10388-020-00718-9.
- 18 Miyata H, Yamasaki M, Makino T. et al Clinical Outcome of Esophagectomy in Elderly Patients With and Without Neoadjuvant Therapy for Thoracic Esophageal Cancer. Ann Surg Oncol 2015; 22 (Suppl. 03) S794-S801 . doi:10.1245/s10434-015-4769-8
- 19 Biere SS, van Berge Henegouwen MI, Maas KW. et al Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial. Lancet 2012; 379: 1887-1892 . doi:10.1016/s0140-6736(12)60516-9
- 20 Mariette C, Markar S, Dabakuyo-Yonli TS. et al. Health-related Quality of Life Following Hybrid Minimally Invasive Versus Open Esophagectomy for Patients With Esophageal Cancer, Analysis of a Multicenter, Open-label, Randomized Phase III Controlled Trial: The MIRO Trial. Ann Surg 2019; DOI: 10.1097/sla.0000000000003559.
- 21 van der Sluis PC, van der Horst S, May AM. et al Robot-assisted Minimally Invasive Thoracolaparoscopic Esophagectomy Versus Open Transthoracic Esophagectomy for Resectable Esophageal Cancer: A Randomized Controlled Trial. Ann Surg 2019; 269: 621-630 . doi:10.1097/sla.0000000000003031
- 22 van Workum F, van der Maas J, van den Wildenberg FJ. et al Improved Functional Results After Minimally Invasive Esophagectomy: Intrathoracic Versus Cervical Anastomosis. Ann Thorac Surg 2017; 103: 267-273 . doi:10.1016/j.athoracsur.2016.07.010
- 23 Kauppila JH, Xie S, Johar A. et al Meta-analysis of health-related quality of life after minimally invasive versus open oesophagectomy for oesophageal cancer. Br J Surg 2017; 104: 1131-1140 . doi:10.1002/bjs.10577
- 24 van Hagen P, Hulshof MC, van Lanschot JJ. et al Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012; 366: 2074-2084 . doi:10.1056/NEJMoa1112088
- 25 Walter F, Bockle D, Schmidt-Hegemann NS. et al Clinical outcome of elderly patients (>/= 70 years) with esophageal cancer undergoing definitive or neoadjuvant radio(chemo)therapy: a retrospective single center analysis. Radiat Oncol 2018; 13: 93 . doi:10.1186/s13014-018-1044-8
- 26 Guttmann DM, Mitra N, Metz JM. et al Neoadjuvant chemoradiation is associated with improved overall survival in older patients with esophageal cancer. J Geriatr Oncol 2018; 9: 40-46 . doi:10.1016/j.jgo.2017.08.010
- 27 Stahl M, Stuschke M, Lehmann N. et al Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 2005; 23: 2310-2317 . doi:10.1200/jco.2005.00.034
- 28 Won E, Ilson DH. Management of localized esophageal cancer in the older patient. Oncologist 2014; 19: 367-374 . doi:10.1634/theoncologist.2013-0178
- 29 Lorenzen S, Pauligk C, Homann N. et al Feasibility of perioperative chemotherapy with infusional 5-FU, leucovorin, and oxaliplatin with (FLOT) or without (FLO) docetaxel in elderly patients with locally advanced esophagogastric cancer. Br J Cancer 2013; 108: 519-526 . doi:10.1038/bjc.2012.588
- 30 Bleiberg H, Conroy T, Paillot B. et al Randomised phase II study of cisplatin and 5-fluorouracil (5-FU) versus cisplatin alone in advanced squamous cell oesophageal cancer. Eur J Cancer 1997; 33: 1216-1220 . doi:10.1016/s0959-8049(97)00088-9
- 31 Shah MA, Adenis A, Enzinger PC. et al Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: Phase 3 KEYNOTE-181 study. Journal of Clinical Oncology 2019; 37: 4010-4010 . doi:10.1200/JCO.2019.37.15_suppl.4010
- 32 Kato K, Shah MA, Enzinger P. et al KEYNOTE-590: Phase III study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer. Future Oncol 2019; 15: 1057-1066 . doi:10.2217/fon-2018-0609
- 33 Meindl-Beinker NM, Betge J, Gutting T. et al A multicenter open-label phase II trial to evaluate nivolumab and ipilimumab for 2nd line therapy in elderly patients with advanced esophageal squamous cell cancer (RAMONA). BMC Cancer 2019; 19: 231 . doi:10.1186/s12885-019-5446-2
- 34 Fujiwara Y, Fukuda S, Tsujie M. et al Effects of age on survival and morbidity in gastric cancer patients undergoing gastrectomy. World J Gastrointest Oncol 2017; 9: 257-262 . doi:10.4251/wjgo.v9.i6.257
- 35 Jeong O, Park YK, Ryu SY. et al Effect of age on surgical outcomes of extended gastrectomy with D2 lymph node dissection in gastric carcinoma: prospective cohort study. Ann Surg Oncol 2010; 17: 1589-1596 . doi:10.1245/s10434-010-0916-4
- 36 Zhou CJ, Chen FF, Zhuang CL. et al Feasibility of radical gastrectomy for elderly patients with gastric cancer. Eur J Surg Oncol 2016; 42: 303-311 . doi:10.1016/j.ejso.2015.11.013
- 37 Choi YY, Bae JM, An JY. et al Laparoscopic gastrectomy for advanced gastric cancer: are the long-term results comparable with conventional open gastrectomy? A systematic review and meta-analysis. J Surg Oncol 2013; 108: 550-556 . doi:10.1002/jso.23438
- 38 Liu D, Liang L, Liu L. et al. Short-term outcomes and prognosis of laparoscopy-assisted total gastrectomy in elderly patients with stomach cancer. Surg Endosc 2020; DOI: 10.1007/s00464-019-07338-0.
- 39 Watanabe M, Iwatsuki M, Iwagami S. et al Prognostic nutritional index predicts outcomes of gastrectomy in the elderly. World J Surg 2012; 36: 1632-1639 . doi:10.1007/s00268-012-1526-z
- 40 Mislang AR, Di Donato S, Hubbard J. et al Nutritional management of older adults with gastrointestinal cancers: An International Society of Geriatric Oncology (SIOG) review paper. J Geriatr Oncol 2018; 9: 382-392 . doi:10.1016/j.jgo.2018.01.003
- 41 Cunningham D, Allum WH, Stenning SP. et al Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006; 355: 11-20 . doi:10.1056/NEJMoa055531
- 42 Ychou M, Boige V, Pignon JP. et al Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 2011; 29: 1715-1721 . doi:10.1200/jco.2010.33.0597
- 43 Al-Batran SE, Homann N, Pauligk C. et al Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet 2019; 393: 1948-1957 . doi:10.1016/s0140-6736(18)32557-1
- 44 Trumper M, Ross PJ, Cunningham D. et al Efficacy and tolerability of chemotherapy in elderly patients with advanced oesophago-gastric cancer: A pooled analysis of three clinical trials. Eur J Cancer 2006; 42: 827-834 . doi:10.1016/j.ejca.2005.08.044
- 45 Jatoi A, Foster NR, Egner JR. et al Older versus younger patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and stomach: a pooled analysis of eight consecutive North Central Cancer Treatment Group (NCCTG) trials. Int J Oncol 2010; 36: 601-606 . doi:10.3892/ijo_00000535
- 46 Cunningham D, Starling N, Rao S. et al Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008; 358: 36-46 . doi:10.1056/NEJMoa073149
- 47 Kang YK, Kang WK, Shin DB. et al Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol 2009; 20: 666-673 . doi:10.1093/annonc/mdn717
- 48 Okines AF, Norman AR, McCloud P. et al Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer. Ann Oncol 2009; 20: 1529-1534 . doi:10.1093/annonc/mdp047
- 49 Shitara K, Doi T, Dvorkin M. et al Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2018; 19: 1437-1448 . doi:10.1016/s1470-2045(18)30739-3
- 50 Al-Batran SE, Hartmann JT, Probst S. et al Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol 2008; 26: 1435-1442 . doi:10.1200/jco.2007.13.9378
- 51 Hwang IG, Ji JH, Kang JH. et al A multi-center, open-label, randomized phase III trial of first-line chemotherapy with capecitabine monotherapy versus capecitabine plus oxaliplatin in elderly patients with advanced gastric cancer. J Geriatr Oncol 2017; 8: 170-175 . doi:10.1016/j.jgo.2017.01.002
- 52 Hall PS, Swinson D, Waters JS. et al Optimizing chemotherapy for frail and elderly patients (pts) with advanced gastroesophageal cancer (aGOAC): The GO2 phase III trial. Journal of Clinical Oncology 2019; 37: 4006-4006 . doi:10.1200/JCO.2019.37.15_suppl.4006
- 53 Al-Batran SE, Pauligk C, Homann N. et al The feasibility of triple-drug chemotherapy combination in older adult patients with oesophagogastric cancer: a randomised trial of the Arbeitsgemeinschaft Internistische Onkologie (FLOT65+). Eur J Cancer 2013; 49: 835-842 . doi:10.1016/j.ejca.2012.09.025
- 54 Bang YJ, Van Cutsem E, Feyereislova A. et al Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010; 376: 687-697 . doi:10.1016/s0140-6736(10)61121-x
- 55 Fuchs CS, Tomasek J, Yong CJ. et al Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2014; 383: 31-39 . doi:10.1016/s0140-6736(13)61719-5
- 56 Wilke H, Muro K, Van Cutsem E. et al Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 2014; 15: 1224-1235 . doi:10.1016/s1470-2045(14)70420-6
- 57 Shitara K, Ozguroglu M, Bang YJ. et al Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet 2018; 392: 123-133 . doi:10.1016/s0140-6736(18)31257-1
- 58 Chika N, Fukuchi M, Suzuki O. et al. [Incidence and Characteristics of Mismatch Repair Protein Deficiency in Elderly Gastric Cancer Patients]. Gan To Kagaku Ryoho 2016; 43: 1298-1300
- 59 Siegel RL, Miller KD, Fedewa SA. et al Colorectal cancer statistics, 2017. CA Cancer J Clin 2017; 67: 177-193 . doi:10.3322/caac.21395
- 60 Aparicio T, Schischmanoff O, Poupardin C. et al Deficient mismatch repair phenotype is a prognostic factor for colorectal cancer in elderly patients. Dig Liver Dis 2013; 45: 245-250 . doi:10.1016/j.dld.2012.09.013
- 61 Takahashi Y, Mizuno KI, Takahashi K. et al Long-term outcomes of colorectal endoscopic submucosal dissection in elderly patients. Int J Colorectal Dis 2017; 32: 567-573 . doi:10.1007/s00384-016-2719-y
- 62 Ueno H, Mochizuki H, Hashiguchi Y. et al Risk factors for an adverse outcome in early invasive colorectal carcinoma. Gastroenterology 2004; 127: 385-394 . doi:10.1053/j.gastro.2004.04.022
- 63 Mitry E, Bouvier AM, Esteve J. et al Improvement in colorectal cancer survival: a population-based study. Eur J Cancer 2005; 41: 2297-2303 . doi:10.1016/j.ejca.2005.01.028
- 64 Ketelaers SHJ, Fahim M, Rutten HJT. et al. When and how should surgery be performed in senior colorectal cancer patients?. Eur J Surg Oncol 2020; DOI: 10.1016/j.ejso.2020.01.007.
- 65 Claassen YHM, Bastiaannet E, van Eycken E. et al Time trends of short-term mortality for octogenarians undergoing a colorectal resection in North Europe. Eur J Surg Oncol 2019; 45: 1396-1402 . doi:10.1016/j.ejso.2019.03.041
- 66 Millan M, Merino S, Caro A. et al Treatment of colorectal cancer in the elderly. World J Gastrointest Oncol 2015; 7: 204-220 . doi:10.4251/wjgo.v7.i10.204
- 67 Buunen M, Veldkamp R, Hop WC. et al Survival after laparoscopic surgery versus open surgery for colon cancer: long-term outcome of a randomised clinical trial. Lancet Oncol 2009; 10: 44-52 . doi:10.1016/s1470-2045(08)70310-3
- 68 Zhou S, Wang X, Zhao C. et al Laparoscopic vs open colorectal cancer surgery in elderly patients: short- and long-term outcomes and predictors for overall and disease-free survival. BMC Surg 2019; 19: 137 . doi:10.1186/s12893-019-0596-3
- 69 Green BL, Marshall HC, Collinson F. et al Long-term follow-up of the Medical Research Council CLASICC trial of conventional versus laparoscopically assisted resection in colorectal cancer. Br J Surg 2013; 100: 75-82 . doi:10.1002/bjs.8945
- 70 Cone MM, Herzig DO, Diggs BS. et al Dramatic decreases in mortality from laparoscopic colon resections based on data from the Nationwide Inpatient Sample. Arch Surg 2011; 146: 594-599 . doi:10.1001/archsurg.2011.79
- 71 Moertel CG, Fleming TR, Macdonald JS. et al Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 1990; 322: 352-358 . doi:10.1056/nejm199002083220602
- 72 Andre T, Boni C, Mounedji-Boudiaf L. et al Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004; 350: 2343-2351 . doi:10.1056/NEJMoa032709
- 73 Sanoff HK, Carpenter WR, Sturmer T. et al Effect of adjuvant chemotherapy on survival of patients with stage III colon cancer diagnosed after age 75 years. J Clin Oncol 2012; 30: 2624-2634 . doi:10.1200/jco.2011.41.1140
- 74 Folprecht G, Cunningham D, Ross P. et al Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol 2004; 15: 1330-1338 . doi:10.1093/annonc/mdh344
- 75 Popescu RA, Norman A, Ross PJ. et al Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older. J Clin Oncol 1999; 17: 2412-2418 . doi:10.1200/jco.1999.17.8.2412
- 76 Seymour MT, Thompson LC, Wasan HS. et al Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet 2011; 377: 1749-1759 . doi:10.1016/s0140-6736(11)60399-1
- 77 Van Cutsem E, Mayer RJ, Laurent S. et al The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer. Eur J Cancer 2018; 90: 63-72 . doi:10.1016/j.ejca.2017.10.009
- 78 Folprecht G, Seymour MT, Saltz L. et al Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials. J Clin Oncol 2008; 26: 1443-1451 . doi:10.1200/jco.2007.14.0509
- 79 Aparicio T, Lavau-Denes S, Phelip JM. et al Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001-02). Ann Oncol 2016; 27: 121-127 . doi:10.1093/annonc/mdv491
- 80 Sastre J, Aranda E, Gravalos C. et al First-line single-agent cetuximab in elderly patients with metastatic colorectal cancer. A phase II clinical and molecular study of the Spanish group for digestive tumor therapy (TTD). Crit Rev Oncol Hematol 2011; 77: 78-84 . doi:10.1016/j.critrevonc.2009.11.005
- 81 Sastre J, Gravalos C, Rivera F. et al First-line cetuximab plus capecitabine in elderly patients with advanced colorectal cancer: clinical outcome and subgroup analysis according to KRAS status from a Spanish TTD Group Study. Oncologist 2012; 17: 339-345 . doi:10.1634/theoncologist.2011-0406
- 82 Maughan TS, Adams RA, Smith CG. et al Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 2011; 377: 2103-2114 . doi:10.1016/s0140-6736(11)60613-2
- 83 Folprecht G, Kohne C, Bokemeyer C. et al Cetuximab and 1st line chemotherapy in elderly and younger patients with metastatic colorectal cancer (mCRC): a pooled analysis of the CRYSTAL and OPUS studies. Ann Oncol 2010; 21 (Suppl. 08) abstract 597P
- 84 Jehn CF, Boning L, Kroning H. et al Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer. Br J Cancer 2012; 106: 274-278 . doi:10.1038/bjc.2011.554
- 85 Douillard JY, Siena S, Cassidy J. et al Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol 2014; 25: 1346-1355 . doi:10.1093/annonc/mdu141
- 86 Sastre J, Massuti B, Pulido G. et al First-line single-agent panitumumab in frail elderly patients with wild-type KRAS metastatic colorectal cancer and poor prognostic factors: A phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours. Eur J Cancer 2015; 51: 1371-1380 . doi:10.1016/j.ejca.2015.04.013
- 87 Battaglin F, Schirripa M, Buggin F. et al The PANDA study: a randomized phase II study of first-line FOLFOX plus panitumumab versus 5FU plus panitumumab in RAS and BRAF wild-type elderly metastatic colorectal cancer patients. BMC Cancer 2018; 18: 98 . doi:10.1186/s12885-018-4001-x
- 88 Cunningham D, Lang I, Marcuello E. et al 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 . doi:10.1016/s1470-2045(13)70154-2
- 89 Price TJ, Zannino D, Wilson K. et al 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 . doi:10.1093/annonc/mdr488