Volume 14, Issue 4 ( December 2022 2022)                   Iranian Journal of Blood and Cancer 2022, 14(4): 116-124 | Back to browse issues page

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Colombo A, Porretto C M, Fazio I, Sciacchitano T, Mazzonello A. “How should we treat older patients with Metastatic Colorectal Cancer, A Review”. Iranian Journal of Blood and Cancer 2022; 14 (4) :116-124
URL: http://ijbc.ir/article-1-1326-en.html
“How should we treat older patients with Metastatic Colorectal Cancer, A Review”
Alfredo Colombo * 1, Concetta Maria Porretto2 , Ivan Fazio3 , Tommaso Sciacchitano2 , Antonella Mazzonello4
1- Oncology Unit C.D.C Macchiarella - Palermo-Italy , alfredocolo63@gmail.com
2- Oncology Unit C.D.C Macchiarella - Palermo-Italy
3- Radiotherapy Unit CDC Macchiarella - Palermo- Italy
4- Radiotherapy Unit CDC Macchiarella
Abstract:   (547 Views)
Nearly 50 % of newly diagnosed colorectal cancer, affect people over 70 years of age. Inclusion of older patients in clinical trials has been extremely rare. As a result, there is debate on how to manage these patients because it is still unclear how to balance the therapeutic advantages and toxicities. For patients who do not have comorbid conditions, with performance status (P.S.) 0–1, treatment guidelines are comparable to those for younger ones. Chemotherapy is an option for older patients; however, a full geriatric evaluation is recommended. Bevacizumab, an anti-vascular epithelial growth factor (anti-VEGF), combined with chemotherapy has become a standard of care in older patients. Anti-epidermal growth factor receptor (anti-EGFR) treatment is proposed both as monotherapy in the third-line or with chemotherapy in first or second line. Clinical trials that compared chemotherapy alone versus doublet chemotherapy plus anti-EGFR in older patients found that age is not an absolute contraindication for using anti-EGFR in first or second line. In fit older patients, anti-EGFR monotherapy in the first second or third line has demonstrated feasibility and antitumor efficacy. The major side effect is cutaneous rash which is easily managed. However, treatment in older patients should be carried out and be based on co-morbidities.
 
Keywords: Metastatic colorectal cancer, Anti-EGFR, Chemotherapy, Toxicities
Full-Text [PDF 331 kb]   (509 Downloads)    
: Review Article | Subject: Adults Hematology & Oncology
Received: 2022/11/10 | Accepted: 2022/12/12 | Published: 2022/12/28
References
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68:394-424. [DOI:10.3322/caac.21492]
2. Les cancers en France, Les Données, INCa. édition https://www.e-cancer.fr/content/download/255246/3573612/file/Cancers_en_FranceEssentiel_Faits_et_chiffres- 2018.pdf; 2018.
3. Holleczek B, Rossi S, Domenic A, et al. On-going improvement and persistent differences in the survival for patients with colon and rectumcancer across Europe 1999- 2007 - results from the EUROCARE-5 study. Eur J Cancer 2015; 51:2158-68. [DOI:10.1016/j.ejca.2015.07.024]
4. Gouverneur A, Salvo F, Berdai D,Moore N, Fourrier-Reglat A, Noize P. Inclusion of elderly or frail patients in randomized controlled trials of targeted therapies for the treatment of metastatic colorectal cancer: a systematic review. J Geriatr Oncol 2018; 9:15-23. [DOI:10.1016/j.jgo.2017.08.001]
5. Papamichael D, Audisio RA, Glimelius B, et al. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol 2015; 26:463-76. [DOI:10.1093/annonc/mdu253]
6. Jarrett PG, Rockwood K, Carver D, Stolee P, Cosway S. Illness presentation in elderly patients. Arch Intern Med 1995; 155:1060-4. [DOI:10.1001/archinte.1995.00430100086010]
7. Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 2016;27:1386-422. [DOI:10.1093/annonc/mdw235]
8. Soubeyran P, Bellera C, Goyard J, et al. Validation of the G8 screening tool in geriatric oncology: the ONCODAGE project. J Clin Oncol 2011; 29:9001. [DOI:10.1200/jco.2011.29.15_suppl.9001]
9. Soubeyran P, Bellera C, Goyard J, et al. Screening for vulnerability in older cancer patients the ONCODAGE prospective multicenter cohort study. PLoS One 2014;9:e115060. [DOI:10.1371/journal.pone.0115060]
10. Shafiei M, Yoon R, McLachlan A, Boddy A, Beale P, Blinman P. Pharmacokinetics of anticancer drugs used in treatment of older adults with colorectal Cancer: a systematic review. Ther Drug Monit 2019; 41:553-60. [DOI:10.1097/FTD.0000000000000635]
11. 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; 118:3377-86. [DOI:10.1002/cncr.26646]
12. Seymour MT, Thompson LC, Wasan HS, et al. Chemotherapy options in elderly and rail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomized factorial trial. Lancet 2011; 377:1749-59. [DOI:10.1016/S0140-6736(11)60399-1]
13. 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; 27:121-7. [DOI:10.1093/annonc/mdv491]
14. Aparicio T, Jouve JL, Teillet L, et al. 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; 31:1464-70. [DOI:10.1200/JCO.2012.42.9894]
15. Aparicio T, Gargot D, Teillet L, et al. Geriatric factors analyses from FFCD 2001-02 phase III study of first-line chemotherapy for elderlymetastatic colorectal cancer patients. Eur J Cancer 2017; 74:98-108. [DOI:10.1016/j.ejca.2016.09.029]
16. 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, randomized phase 3 trial. Lancet Oncol 2013;14: 1077-85. [DOI:10.1016/S1470-2045(13)70154-2]
17. Aparicio T, Bouche O, Taieb J, et al. Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial-PRODIGE 20 study results. Ann Oncol 2018; 29:2270. https://doi.org/10.1093/annonc/mdx529 [DOI:10.1093/annonc/mdx808]
18. Aparicio T, Bouche O, Francois E, et al. Geriatric analysis from PRODIGE 20 randomized phase II trial evaluating bevacizumab + chemotherapy versus chemotherapy alone in older patients with untreated metastatic colorectal cancer. Eur J Cancer 2018; 97:16-24. [DOI:10.1016/j.ejca.2018.03.030]
19. Landre T, Uzzan B, Nicolas P, et al. Doublet chemotherapy vs. single-agent therapy with 5FU in elderly patients with metastatic colorectal cancer. A meta-analysis. Int J Colorectal Dis 2015; 30:1305-10. [DOI:10.1007/s00384-015-2296-5]
20. Landre T, Maillard E, Taleb C, et al. Impact of the addition of bevacizumab, oxaliplatin, or irinotecan to fluoropyrimidin in the first-line treatment of metastatic colorectal cancer in elderly patients. Int J Colorectal Dis 2018; 33:1125-30. [DOI:10.1007/s00384-018-3053-3]
21. Van Cutsem E, Kohne CH, Lang I, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol 2011; 29:2011-9. [DOI:10.1200/JCO.2010.33.5091]
22. Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26:1626-34. [DOI:10.1200/JCO.2007.14.7116]
23. Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 2010; 28:4697-705. https://doi.org/10.1200/jco.2010.28.15_suppl.3528 [DOI:10.1200/JCO.2009.27.4860]
24. VanderWalde N, Jagsi R, Dotan E, et al. NCCN guidelines insights: older adult oncology, version 2.2016. J Natl Compr Canc Netw 2016; 14:1357-70. [DOI:10.6004/jnccn.2016.0146]
25. Folprecht G, Köhne 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; 21:194.
26. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomized, open-label, phase 3 trial. Lancet Oncol 2014; 15:1065-75. [DOI:10.1016/S1470-2045(14)70330-4]
27. 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; 25:1346-55. [DOI:10.1093/annonc/mdu141]
28. Douillard J, Siena S, Peeters M, Koukakis R, Terwey J, Tabernero J. Impact of baseline age on efficacy and safety of first-line panitumumab + FOLFOX4 vs FOLFOX4 treatment. Ann Oncol 2014;25 iv187. [DOI:10.1093/annonc/mdu333.49]
29. Jehn CF, Boning L, Kroning H, Possinger K, Luftner D. Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer. Br J Cancer 2012;106: 274-8. [DOI:10.1038/bjc.2011.554]
30. Peeters M, Price TJ, Cervantes A, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 2010; 28:4706-13. https://doi.org/10.1200/JCO.2009.27.6055 [DOI:10.1200/jco.2010.28.15_suppl.3565]
31. PeetersM, Price T, Cervantes A, et al. Impact of baseline covariates and prior therapy on the efficacy of second-line panitumumab + FOLFIRI vs FOLFIRI treatment. Ann Oncol 2014;25 (iv187-iv8). [DOI:10.1093/annonc/mdu333.50]
32. 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: 339-45. [DOI:10.1634/theoncologist.2011-0406]
33. 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 randomized phase 3 MRC COIN trial. Lancet 2011; 377:2103-14. [DOI:10.1016/S0140-6736(11)60613-2]
34. MéndezMéndez JC, Ramos M, De la Cámara Gómez JC, et al. First-line panitumumab plus capecitabine for the treatment of elderly patientswith wild-type KRASmetastatic colorectal cancer: preliminary results of the phase II, PANEL GITuD-2011-01 study. Ann Oncol 2017;28. [DOI:10.1093/annonc/mdx393.079]
35. Kienle DL, Dietrich D, Ribi K, et al. Cetuximab monotherapy and cetuximab plus capecitabine as first-line treatment in older patients with RAS- and BRAF wild-type metastatic colorectal cancer. Results of the multicenter phase II trial SAKK 41/10. J Geriatr Oncol 2019; 10:304-10. [DOI:10.1016/j.jgo.2018.11.011]
36. Sastre J, Massuti B, Pulido G, et al. First-line single-agent panitumumab in frail elderly patientswithwild-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; 51:1371-80. [DOI:10.1016/j.ejca.2015.04.013]
37. Ohta K, Kato T, Goto M, et al. Phase II study of panitumumab monotherapy in chemotherapy-naïve frail or elderly patients with unresectable, RAS wild-type colorectal cancer: OGSG 1602. ASCO Gastrointestinal Cancers Symposium 2020; 38:106 January 23-25. [DOI:10.1200/JCO.2020.38.4_suppl.106]
38. Pietrantonio F, Cremolini C, Aprile G, et al. Single-agent Panitumumab in frail elderly patients with advanced RAS and BRAF wild-type colorectal Cancer: challenging drug label to light up new Hope. Oncologist 2015; 20:1261-5. [DOI:10.1634/theoncologist.2015-0171]
39. Jonker DJ, O'Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007; 357:2040-8. [DOI:10.1056/NEJMoa071834]
40. Van Cutsem E, Peeters M, Siena S, 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: 1658-64. [DOI:10.1200/JCO.2006.08.1620]
41. Price TJ, Peeters M, Kim TW, et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomized, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol 2014; 15:569-79. [DOI:10.1016/S1470-2045(14)70118-4]
42. Rouyer M, Fourrier-Réglat A, Noize P, et al. Efficacité et sécurité d'emploi du cétuximab en traitement de 1re ligne du cancer colorectal métastatique chez les sujets âgés: résultats de la cohorte EREBUS. Rev Epidemiol Sante Publique 2016; 64 (S271-S2). [DOI:10.1016/j.respe.2016.04.008]
43. Jehn CF, Boning L, Kroning H, Pezzutto A, Luftner D. Influence of comorbidity, age and performance status on treatment efficacy and safety of cetuximab plus irinotecan in irinotecan-refractory elderly patientswithmetastatic colorectal cancer. Eur J Cancer 2014; 50:1269-75. [DOI:10.1016/j.ejca.2014.01.005]
44. Rosati G, Pinto C, Di Fabio F, et al. Quality of life, compliance, safety and effectiveness in fit older metastatic colorectal patients with cancer treated in first-line with chemotherapy plus cetuximab: a restrospective analysis from the ObservEr study. J Geriatr Oncol 2018; 9:243-8. [DOI:10.1016/j.jgo.2018.01.009]
45. 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]
46. Feliu J, Salud A, Losada EP, et al. First-line treatment with panitumumab plus FOLFIRI in elderly patients with RAS/BRAF wild-type unresectable metastatic colorectal cancer and good performance status: OPALO trial. J Clin Oncol 2018; 36:3618. [DOI:10.1200/JCO.2018.36.15_suppl.TPS3618]
47. Tebbutt NC, Steer CB, Sjoquist KM, et al. MONARCC: a randomized phase II study of panitumumabmonotherapy and panitumumab plus 5 fluorouracil as first-line therapy for RAS and BRAF wild type metastatic colorectal cancer: an AGITG clinical trial. ASCO Gastrointestinal Cancers Symposium 2020;38: TPS271 January 23-25. [DOI:10.1200/JCO.2020.38.4_suppl.TPS271]
48. Canoui-Poitrine F, Lievre A, Dayde F, et al. Inclusion of older patients with Cancer in clinical trials: the SAGE prospective multicenter cohort survey. Oncologist 2019;24 (e1351-e9). [DOI:10.1634/theoncologist.2019-0166]
49. Retornaz F, Guillem O, Rousseau F, et al. Predicting chemotherapy toxicity and death in older adults with Colon Cancer: results of MOST study. Oncologist 2020;25(1): e85-93. https://doi.org/10.1634/theoncologist.2019-0241 [DOI:10.1634/theoncologist.2019-0241.]
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