Comparative Effectiveness of Chemotherapy in Elderly Patients with Metastatic Colorectal Cancer
Treatment advances have improved outcomes in clinical trials of patients with metastatic colorectal cancer (mCRC). Less is known about these effects for patients in real-world settings. This study evaluated treatment patterns and survival in older, demographically diverse patients with mCRC.
A retrospective cohort analysis was performed for 4,250 patients from January 1, 2000 to December 31, 2007 using linked Surveillance, Epidemiology, and End Results-Medicare database. Patients were ≥66 years, enrolled in Medicare parts A and B, and received first-line treatment with fluorouracil and leucovorin (5-FU/LV), capecitabine (CAP), 5-FU/LV plus oxaliplatin (FOLFOX), or CAP and oxaliplatin (CAPOX). Cox regression with backward elimination and propensity score-weighted Cox regression estimated relative risk of death. Date of last follow-up was December 2009. Statistical comparisons were made between 5-FU/LV vs. CAP and FOLFOX vs. CAPOX.
Compared to 5-FU/LV, patients treated with CAP were older (mean age 78 vs. 76; P < 0.0001) and more likely female (61 vs. 54 %; P = 0.0017), while patients receiving CAPOX and FOLFOX were similar in age (mean age 74 vs. 73; P = 0.0924). Complications requiring medical resource utilization following initiation of therapy were significantly higher among patients administered with 5-FU/LV (54 %) vs. CAP (17 %; P < 0.0001) and FOLFOX (75 %) vs. CAPOX (57 %; P < 0.0001). The multivariate analysis revealed no significant differences in survival between 5-FU/LV and CAP and between FOLFOX and CAPOX.
Overall survival was comparable between CAP and 5-FU/LV and between CAPOX and FOLFOX with fewer complications requiring medical resource utilization associated with CAP and CAPOX, thus confirming clinical trial results.
- Howlader N, et al. SEER Cancer Statistics Review, 1975–2008. 2011 [based on November 2010 SEER data submission, posted to the SEER web site 2011]. Available from: http://seer.cancer.gov/csr/1975_2008/. Accessed 6 Feb 2012.
- Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;1:10–29. CrossRef
- Douillard JY, Bennouna J, Senellart H. Is XELOX equivalent to FOLFOX or other continuous-infusion 5-fluorouracil chemotherapy in metastatic colorectal cancer? Clin Color Cancer. 2008;3:206–11. CrossRef
- Koukourakis GV, et al. Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review. Molecules. 2008;8:1897–922. CrossRef
- Thirion P, et al. Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: an updated meta-analysis. J Clin Oncol. 2004;18:3766–75.
- Goldberg RM, et al. Randomized controlled trial of reduced-dose bolus fluorouracil plus leucovorin and irinotecan or infused fluorouracil plus leucovorin and oxaliplatin in patients with previously untreated metastatic colorectal cancer: a North American Intergroup Trial. J Clin Oncol. 2006;21:3347–53. CrossRef
- Braun AH, et al. New systemic frontline treatment for metastatic colorectal carcinoma. Cancer. 2004;8:1558–77. CrossRef
- Van Cutsem E, et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001;21:4097–106.
- Van Cutsem E, et al. Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials. Br J Cancer. 2004;6:1190–7. CrossRef
- Welles L, Hochster H, Ramanathan R, et al. Preliminary results of a randomized study of the safety and tolerability of three oxaliplatin-based regimens as first-line treatment for advanced colorectal cancer (CRC) (“TREE” study). Proc Am Soc Clin Oncol. 2004;23:254 (Abstract #3537).
- Cassidy J, Clarke S, and Diaz-Rubio E. First efficacy and safety results from XELOX-I/NO16966, a randomized 2 × 2 factorial phase III trial of XELOX vs. FOLFOX4 + bevacizumab or placebo in first-line metastatic colorectal cancer (MCRC), in Annual Meeting of the European Society of Medical Oncology2006: Istanbul, Turkey.
- Ducreux M, et al. Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) as first-line treatment for metastatic colorectal cancer. Int J Cancer. 2011;128(3):682–90. CrossRef
- Diaz-Rubio E, et al. Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic colorectal cancer: final report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial. J Clin Oncol. 2007;27:4224–30. CrossRef
- Porschen R, et al. Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol. 2007;27:4217–23. CrossRef
- Comella P, et al. Biweekly oxaliplatin combined with oral capecitabine (OXXEL regimen) as first-line treatment of metastatic colorectal cancer patients: a Southern Italy Cooperative Oncology Group phase II study. Cancer Chemother Pharmacol. 2005;5:481–6. CrossRef
- Comella P, et al. Capecitabine plus oxaliplatin for the first-line treatment of elderly patients with metastatic colorectal carcinoma: final results of the Southern Italy Cooperative Oncology Group Trial 0108. Cancer. 2005;2:282–9. CrossRef
- Goldberg RM, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004;1:23–30.
- Cassidy J, et al. XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results. Br J Cancer. 2011;1:58–64. CrossRef
- Arkenau HT, et al. Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer: a pooled analysis of randomized trials. J Clin Oncol. 2008;36:5910–7. CrossRef
- Hutchins LF, et al. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999;27:2061–7. CrossRef
- Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA. 2004;22:2720–6. CrossRef
- Townsley CA, Selby R, Siu LL. Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J Clin Oncol. 2005;13:3112–24. CrossRef
- Chagpar R, et al. Adherence to stage-specific treatment guidelines for patients with colon cancer. J Clin Oncol. 2012;9:972–9. CrossRef
- Schrag D, et al. Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst. 2001;11:850–7. CrossRef
- Ayanian JZ, et al. Use of adjuvant chemotherapy and radiation therapy for colorectal cancer in a population-based cohort. J Clin Oncol. 2003;7:1293–300. CrossRef
- Kahn KL, et al. Adjuvant chemotherapy use and adverse events among older patients with stage III colon cancer. JAMA. 2010;11:1037–45. CrossRef
- O’Grady MA, et al. Assessing compliance with national comprehensive cancer network guidelines for elderly patients with stage III colon cancer: the Fox Chase Cancer Center Partners' initiative. Clin Colorectal Cancer. 2011;2:113–6. CrossRef
- Warren JL, et al. Overview of the SEER-Medicare data: content, research applications, and generalizability to the United States elderly population. Med Care. 2002;8(Suppl:IV):3–18.
- Potosky AL, et al. Potential for cancer related health services research using a linked Medicare-tumor registry database. Med Care. 1993;8:732–48.
- Suissa S. Immortal time bias in pharmaco-epidemiology. Am J Epidemiol. 2008;4:492–9. CrossRef
- Warren JL, et al. Utility of the SEER-Medicare data to identify chemotherapy use. Med Care. 2002;8(Suppl:IV):55–61.
- Klabunde CN, et al. A refined comorbidity measurement algorithm for claims-based studies of breast, prostate, colorectal, and lung cancer patients. Ann Epidemiol. 2007;8:584–90. CrossRef
- NCCN, N.C.C.N, Clinical practice guidelines in oncology. <http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf>. Accessed 6 Feb 2012.
- Greenland S. Introduction to stratified analysis. 2nd ed. Philadelphia: Lippincott; 1998.
- Kurth T, et al. Results of multivariable logistic regression, propensity matching, propensity adjustment, and propensity-based weighting under conditions of nonuniform effect. Am J Epidemiol. 2006;3:262–70.
- de Gramont A, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;16:2938–47.
- Giacchetti S, et al. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2000;1:136–47.
- Cassidy J, et al. XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol. 2004;11:2084–91. CrossRef
- Moertel CG, et al. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med. 1995;5:321–6.
- O’Connell MJ, et al. Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol. 1997;1:246–50.
- Investigators, I.M.P.A.O.C.C.T.I. Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Lancet. 1995;8955.
- Wolmark N, et al. The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J Clin Oncol. 1993;10:1879–87.
- Grothey A, et al. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol. 2004;7:1209–14. CrossRef
- Cartwright TH. Treatment decisions after diagnosis of metastatic colorectal cancer. Clin Colorectal Cancer. 2012;3:155–66. CrossRef
- Twelves CJ, et al. Capecitabine/oxaliplatin, a safe and active first-line regimen for older patients with metastatic colorectal cancer: post hoc analysis of a large phase II study. Clin Colorectal Cancer. 2005;2:101–7. CrossRef
- Hoff PM, et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001;8:2282–92.
- Cassidy J, et al. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008;12:2006–12. CrossRef
- Haller DG, et al. Potential regional differences for the tolerability profiles of fluoropyrimidines. J Clin Oncol. 2008;13:2118–23. CrossRef
- Rothenberg ML. Tolerability of fluoropyrimidines in combination with oxaliplatin appears to differ by region. In ASCO: 2008 Gastrointestinal Cancers Symposium. 2008.
- Hochster HS, et al. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol. 2008;21:3523–9. CrossRef
- Schrag D, et al. Who gets adjuvant treatment for stage II and III rectal cancer? Insight from surveillance, epidemiology, and end results–Medicare. J Clin Oncol. 2001;17:3712–8.
- Hershman D, et al. Timing of adjuvant chemotherapy initiation after surgery for stage III colon cancer. Cancer. 2006;11:2581–8. CrossRef
- Dobie SA, et al. Completion of therapy by Medicare patients with stage III colon cancer. J Natl Cancer Inst. 2006;9:610–9. CrossRef
- Lund JL, et al. Identifying specific chemotherapeutic agents in medicare data: a validation study. Med Care. 2012, in press.
- Merrill RM, et al. Survival and treatment for colorectal cancer Medicare patients in two group/staff health maintenance organizations and the fee-for-service setting. Med Care Res Rev. 1999;2:177–96. CrossRef
- Kirsner RS, et al. The effect of medicare health care delivery systems on survival for patients with breast and colorectal cancer. Cancer Epidemiol Biomark Prev. 2006;4:769–73. CrossRef
- Comparative Effectiveness of Chemotherapy in Elderly Patients with Metastatic Colorectal Cancer
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Journal of Gastrointestinal Cancer
Volume 44, Issue 1 , pp 79-88
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- Metastatic colorectal cancer
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