Adjuvant therapy for resected colon cancer in elderly patients
- Hanna K Sanoff, MD, MPH
Hanna K Sanoff, MD, MPH
- Associate Professor
- University of North Carolina at Chapel Hill
Approximately 134,490 new cases of large bowel cancer are diagnosed each year in the United States, of which 95,270 are colon cancers; the remainder arise in the rectum . Global, country-specific incidence rates for colorectal cancer are available through the World Health Organization GLOBOCAN database.
Age is a major risk factor for colorectal cancer (figure 1) . The median age at diagnosis is 71. Approximately 70 percent of cases develop over the age of 65; 40 percent are 75 years or older. The US Census bureau projects that by the year 2030 the number of Americans over age 65 will double . As a result, the number of patients over the age of 70 presenting for colorectal cancer care is expected to rise.
Surgical resection is the only curative treatment for locoregional colon cancer, and outcome is most closely related to the extent of disease at presentation (table 1 and figure 2) . For patients who have undergone potentially curative resection, disease recurrence is thought to arise from clinically occult micrometastases that are present at the time of surgery. Postoperative (adjuvant) systemic chemotherapy is recommended for high-risk patients to eradicate these micrometastases, thereby increasing the cure rate.
This topic review will cover the benefits, risks, and choice of adjuvant chemotherapy for elderly patients with resected colon cancer. A general discussion of the benefits of adjuvant chemotherapy for resected colon and rectal cancer, surgical management and prognosis of colon cancer, chemotherapy considerations in older individuals with advanced colorectal cancer, a compilation of chemotherapy protocols for colorectal cancer, and recommendations for posttreatment follow-up are discussed separately. (See "Adjuvant therapy for resected stage III (node-positive) colon cancer" and "Adjuvant therapy for resected rectal adenocarcinoma" and "Overview of the management of primary colon cancer" and "Therapy for metastatic colorectal cancer in elderly patients and those with a poor performance status" and "Treatment protocols for small and large bowel cancer" and "Surveillance after colorectal cancer resection".)
CHALLENGES SPECIFIC TO THE ELDERLY
The essential principles of treating colon cancer in the elderly are the same as in younger patients. However, for older patients, who may have age-related organ function decline and comorbid conditions that may limit life expectancy, special attention must be paid to the risks of chemotherapy, including both treatment-related toxicity and quality of life issues.
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66:7.
- Ries L, Melbert D, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2006, National Cancer Institute. Bethesda, MD. http://seer.cancer.gov/csr/1975_2006/ (Accessed on March 14, 2011).
- US Interim Projections by Age, Sex, Race, and Hispanic Origin. US Census Burreau, 2004.
- AJCC (American Joint Committee on Cancer) Cancer Staging Manual, 7th edition, Edge, SB, Byrd, DR, Compton, CC, et al (Eds) (Eds), Springer, New York 2010. p.143.
- Sawhney R, Sehl M, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part I. Cancer J 2005; 11:449.
- Sehl M, Sawhney R, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part II. Cancer J 2005; 11:461.
- Yancik R, Wesley MN, Ries LA, et al. Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients: a population-based study. Cancer 1998; 82:2123.
- Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 2006; 24:3187.
- Yancik R, Ries LA. Cancer in older persons. Magnitude of the problem--how do we apply what we know? Cancer 1994; 74:1995.
- Gross CP, McAvay GJ, Guo Z, Tinetti ME. The impact of chronic illnesses on the use and effectiveness of adjuvant chemotherapy for colon cancer. Cancer 2007; 109:2410.
- Hines RB, Chatla C, Bumpers HL, et al. Predictive capacity of three comorbidity indices in estimating mortality after surgery for colon cancer. J Clin Oncol 2009; 27:4339.
- Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol 2011; 29:3457.
- O'Connor ES, Greenblatt DY, LoConte NK, et al. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol 2011; 29:3381.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
- André T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 2009; 27:3109.
- Kahn KL, Adams JL, Weeks JC, et al. Adjuvant chemotherapy use and adverse events among older patients with stage III colon cancer. JAMA 2010; 303:1037.
- Potosky AL, Harlan LC, Kaplan RS, et al. Age, sex, and racial differences in the use of standard adjuvant therapy for colorectal cancer. J Clin Oncol 2002; 20:1192.
- Sundararajan V, Mitra N, Jacobson JS, et al. Survival associated with 5-fluorouracil-based adjuvant chemotherapy among elderly patients with node-positive colon cancer. Ann Intern Med 2002; 136:349.
- Iwashyna TJ, Lamont EB. Effectiveness of adjuvant fluorouracil in clinical practice: a population-based cohort study of elderly patients with stage III colon cancer. J Clin Oncol 2002; 20:3992.
- Schrag D, Cramer LD, Bach PB, Begg CB. Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst 2001; 93:850.
- Jessup JM, Stewart A, Greene FL, Minsky BD. Adjuvant chemotherapy for stage III colon cancer: implications of race/ethnicity, age, and differentiation. JAMA 2005; 294:2703.
- Bradley CJ, Given CW, Dahman B, Fitzgerald TL. Adjuvant chemotherapy after resection in elderly Medicare and Medicaid patients with colon cancer. Arch Intern Med 2008; 168:521.
- Keating NL, Landrum MB, Klabunde CN, et al. Adjuvant chemotherapy for stage III colon cancer: do physicians agree about the importance of patient age and comorbidity? J Clin Oncol 2008; 26:2532.
- Ananda S, Field KM, Kosmider S, et al. Patient age and comorbidity are major determinants of adjuvant chemotherapy use for stage III colon cancer in routine clinical practice. J Clin Oncol 2008; 26:4516.
- Etzioni DA, El-Khoueiry AB, Beart RW Jr. Rates and predictors of chemotherapy use for stage III colon cancer: a systematic review. Cancer 2008; 113:3279.
- Hynes DM, Tarlov E, Durazo-Arvizu R, et al. Surgery and adjuvant chemotherapy use among veterans with colon cancer: insights from a California study. J Clin Oncol 2010; 28:2571.
- Abrams TA, Brightly R, Mao J, et al. Patterns of adjuvant chemotherapy use in a population-based cohort of patients with resected stage II or III colon cancer. J Clin Oncol 2011; 29:3255.
- Sargent DJ, Goldberg RM, Jacobson SD, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med 2001; 345:1091.
- Gill S, Loprinzi CL, Sargent DJ, et al. Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J Clin Oncol 2004; 22:1797.
- 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.
- Feliu J, Escudero P, Llosa F, et al. Capecitabine as first-line treatment for patients older than 70 years with metastatic colorectal cancer: an oncopaz cooperative group study. J Clin Oncol 2005; 23:3104.
- Sanoff HK, Carpenter WR, Stürmer 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.
- Hung A, Mullins CD. Relative effectiveness and safety of chemotherapy in elderly and nonelderly patients with stage III colon cancer: a systematic review. Oncologist 2013; 18:54.
- Cheung WY, Renfro LA, Kerr D, et al. Determinants of Early Mortality Among 37,568 Patients With Colon Cancer Who Participated in 25 Clinical Trials From the Adjuvant Colon Cancer Endpoints Database. J Clin Oncol 2016; 34:1182.
- Zuckerman IH, Rapp T, Onukwugha E, et al. Effect of age on survival benefit of adjuvant chemotherapy in elderly patients with Stage III colon cancer. J Am Geriatr Soc 2009; 57:1403.
- Dobie SA, Baldwin LM, Dominitz JA, et al. Completion of therapy by Medicare patients with stage III colon cancer. J Natl Cancer Inst 2006; 98:610.
- Neugut AI, Matasar M, Wang X, et al. Duration of adjuvant chemotherapy for colon cancer and survival among the elderly. J Clin Oncol 2006; 24:2368.
- Stein BN, Petrelli NJ, Douglass HO, et al. Age and sex are independent predictors of 5-fluorouracil toxicity. Analysis of a large scale phase III trial. Cancer 1995; 75:11.
- Zalcberg J, Kerr D, Seymour L, Palmer M. Haematological and non-haematological toxicity after 5-fluorouracil and leucovorin in patients with advanced colorectal cancer is significantly associated with gender, increasing age and cycle number. Tomudex International Study Group. Eur J Cancer 1998; 34:1871.
- Schmoll HJ, Cartwright T, Tabernero J, et al. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. J Clin Oncol 2007; 25:102.
- Twelves C, Scheithauer W, McKendrick J, et al. Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy. Ann Oncol 2012; 23:1190.
- Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol 2007; 25:1824.
- Cassidy J, Twelves C, Van Cutsem E, et al. First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin. Ann Oncol 2002; 13:566.
- Yoshitani S, Takashima S. Efficacy of postoperative UFT (Tegafur/Uracil) plus PSK therapies in elderly patients with resected colorectal cancer. Cancer Biother Radiopharm 2009; 24:35.
- Goldberg RM, Tabah-Fisch I, Bleiberg H, et al. 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.
- Haller DG, Cassidy J, Tabernero J, et al. Efficacy findings from a randomized phase III trial of capecitabine plus oxaliplatin versus bolus 5-FU/LV for stage III colon cancer (NO16968): No impact of age on disease-free survival (abstract). Data presented at the 2010 ASCO Gastrointestinal Cancers Symposium, Orlando, FL, January 22, 2010.
- Jackson McCleary NA, Meyerhardt J, Green E, et al. Impact of older age on the efficacy of newer adjuvant therapies in >12,500 patients with stage II/III colon cancer: Finedings from the ACCENT database (abstract #4010). J Clin Oncol 2009; 27:170s.
- Haller DG, Tabernero J, Maroun J, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol 2011; 29:1465.
- Sanoff HK, Carpenter WR, Martin CF, et al. Comparative effectiveness of oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy for stage III colon cancer. J Natl Cancer Inst 2012; 104:211.
- Haller DG, O'Connell MJ, Cartwright TH, et al. Impact of age and medical comorbidity on adjuvant treatment outcomes for stage III colon cancer: a pooled analysis of individual patient data from four randomized, controlled trials. Ann Oncol 2015; 26:715.
- Yothers G, O'Connell MJ, Allegra CJ, et al. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol 2011; 29:3768.
- Tournigand C, André T, Bonnetain F, et al. Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: subgroup analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer trial. J Clin Oncol 2012; 30:3353.
- McCleary NJ, Meyerhardt JA, Green E, et al. Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database. J Clin Oncol 2013; 31:2600.
- Sanoff HK, Carpenter WR, Freburger J, et al. Comparison of adverse events during 5-fluorouracil versus 5-fluorouracil/oxaliplatin adjuvant chemotherapy for stage III colon cancer: a population-based analysis. Cancer 2012; 118:4309.
- 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.
- de Gramont A, Bosset JF, Milan C, et al. Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study. J Clin Oncol 1997; 15:808.
- Chambers P, Daniels SH, Thompson LC, Stephens RJ. Chemotherapy dose reductions in obese patients with colorectal cancer. Ann Oncol 2012; 23:748.
- Griggs JJ, Mangu PB, Anderson H, et al. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 2012; 30:1553.
- CHALLENGES SPECIFIC TO THE ELDERLY
- Age-related organ function decline
- Comorbid conditions
- Quality of life issues
- Measures of physical function and reserve
- Use of physical function to guide treatment decisions
- OVERVIEW OF STANDARD ADJUVANT CHEMOTHERAPY FOR COLON CANCER
- Choice of regimen
- - Stage III
- - Stage II
- SAFETY AND EFFICACY OF ADJUVANT CHEMOTHERAPY IN THE ELDERLY
- 5-FU plus leucovorin
- - Toxicity
- Oral fluoropyrimidines
- - Capecitabine
- - UFT
- Oxaliplatin-based regimens
- Irinotecan-based regimens, bevacizumab, and cetuximab
- Summary: choice of regimen
- - Chemotherapy dosing in obese patients
- Use of web-based tools for assessing prognosis and benefit from adjuvant therapy
- POSTTREATMENT SURVEILLANCE AND SECONDARY PREVENTION
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS