Predictors of Treatment Response and Efficacy of FOLFIRI for Second Line Chemotherapy in Metastatic Colorectal Cancer
Article Sidebar
Main Article Content
Abstract
Background: Colorectal cancer is common cancer and leading cause of death. The standard treatment for advanced disease is chemotherapy. However patients who received second line chemotherapy often deteriorated and exhausted after first line treatment. This study aimed to identified predictive factors associated with response to chemotherapy and evaluate efficacy of FOLFIRI chemotherapy. The assessment may help in optimizing the treatment of metastatic colorectal cancer.
Objective: To determine the predictive factors of treatment response and efficacy of FOLFIRI for second line chemotherapy in metastatic colorectal cancer.
Study design: Retrospective case-control study.
Methods: Metastatic colorectal cancer patients in Surin Hospital that were reviewed between January 1st, 2013 and June 30th, 2022 from electronic databases. All patients previously received FOLFOX regimen. Clinical characteristics, laboratory tests, treatments and outcomes were collected in all patients. Exploratory analyses of predictive factors and efficacy of FOLFIRI were performed.
Results: Two hundred and four metastatic colorectal cancer patients in Surin Hospital were recruited and classified into two groups: Responders 54 patients (26.5%) and non-responders 150 patients (73.5%). The predictive factors of response treatment of FOLFIRI were body mass index (BMI) ≥18.5 kg/m2 (OR =6.62, 95%CI: 1.46-29.91, p=0.014), hemoglobin (Hb) ≥13 g/dl (OR=4.04, 95%CI: 1.27-12.83, p=0.018), first line response (CR/PR) (OR=3.80, 95%CI:1.58-9.12, p=0.003 and lymphovascular invasion (LVI) positive (OR=2.40, 95%CI: 1.14-5.07, p=0.021). Progression free survival (PFS) was 8.8 months in responders group and 3.3 months in non-responders group (p<0.001). Median PFS between two groups were 4.1 months (hazard ratio [HR], 0.39; 95%CI, 0.28-0.54; p<0.001). Overall survival (OS) was 30.9 months in responders group and 22.6 months in non-responders group (p=0.002). Median OS between two groups were 23.9 months (HR, 0.42; 95% CI, 0.24-0.74; p=0.003).
Conclusions: Predictive factors for treatment response of second line FOLFIRI chemotherapy in metastatic colorectal cancer were BMI ≥18.5 kg/m2, Hb ≥13 g/dl, first line response (CR/PR) and LVI positive. These factors can be improved outcomes during chemotherapy treatment. The favorable response chemotherapy results in optimized PFS and OS.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
National Insamran W, Sangrajrang S. Cancer Control Program of Thailand. Asian Pac J Cancer Prev 2020;21(3):577-82. doi: 10.31557/APJCP.2020.21.3.577.
Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med 2005;352(5):476-87. doi: 10.1056/NEJMra040958.
Tournigand C, André T, Achille E, Lledo G, Flesh M, Mery-Mignard D, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004;22(2):229-37. doi: 10.1200/JCO.2004.05.113
Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, 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;22(1):23-30. doi: 10.1200/JCO.2004.09.046.
Seymour MT. Fluorouracil, oxaliplatin and CPT-11 (irinotecan), use and sequencing (MRC FOCUS): A 2135-patient randomized trial in advanced colorectal cancer (ACRC)
J Clin Oncol 2005;23(16_suppl):3518. DOI:10.1200/JCO.2005.23.16_SUPPL.3518.
Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007;25(12):1539-44. doi: 10.1200/JCO.2006.09.6305.
Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, 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(31):4706-13. doi: 10.1200/JCO.2009.27.6055.
Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 2008;26(14):2311-9. doi: 10.1200/JCO.2007.13.1193.
André T, Louvet C, Maindrault-Goebel F, Couteau C, Mabro M, Lotz JP, et al. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR. Eur J Cancer 1999;35(9):1343-7. doi: 10.1016/s0959-8049(99)00150-1.
Mabro M, Artru P, André T, Flesch M, Maindrault-Goebel F, Landi B, et al. A phase II study of FOLFIRI-3 (double infusion of irinotecan combined with LV5FU) after FOLFOX in advanced colorectal cancer patients. Br J Cancer 2006;94(9):1287-92. doi: 10.1038/sj.bjc.6603095.
Shitara K, Matsuo K, Yokota T, Takahari D, Shibata T, Ura T, et al. Prognostic factors for metastatic colorectal cancer patients undergoing irinotecan-based second-line chemotherapy. Gastrointest Cancer Res 2011 Sep;4(5-6):168-72.
Suenaga M, Matsusaka S, Ueno M, Yamamoto N, Shinozaki E, Mizunuma N, et al. Predictors of the efficacy of FOLFIRI plus bevacizumab as second-line treatment in metastatic colorectal cancer patients. Surg Today 2011;41(8):1067-74. doi: 10.1007/s00595-010-4432-8.
Heinemann V, von Weikersthal LF, Decker T, Kiani A, Kaiser F, Al-Batran SE, et al. FOLFIRI plus cetuximab or bevacizumab for advanced colorectal cancer: final survival and per-protocol analysis of FIRE-3, a randomised clinical trial. Br J Cancer 2021;124(3):587-94. doi: 10.1038/s41416-020-01140-9.
Guarini C, Grassi T, Pezzicoli G, Porta C. Beyond RAS and BRAF: HER2, a New Actionable Oncotarget in Advanced Colorectal Cancer. Int J Mol Sci 2021;22(13):6813. doi: 10.3390/ijms22136813.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
Ross JS, Torres-Mora J, Wagle N, Jennings TA, Jones DM. Biomarker-based prediction of response to therapy for colorectal cancer: current perspective.Am J Clin Pathol 2010;134(3):478-90. doi: 10.1309/AJCP2Y8KTDPOAORH.
Abdel-Rahman O. Effect of Body Mass Index on 5-FU-Based Chemotherapy Toxicity and Efficacy Among Patients With Metastatic Colorectal Cancer; A Pooled Analysis of 5 Randomized Trials. Clin Colorectal Cancer 2019;18(4):e385-e393. doi: 10.1016/j.clcc.2019.07.005.
Tampellini M, Saini A, Alabiso I, Bitossi R, Brizzi MP, Sculli CM, et al. The role of haemoglobin level in predicting the response to first-line chemotherapy in advanced colorectal cancer patients. Br J Cancer 2006;95(1):13-20. doi: 10.1038/sj.bjc.6603204.
Moreau LC, Rajan R, Thirlwell MP, Alcindor T. Response to chemotherapy in metastatic colorectal cancer after exposure to oxaliplatin in the adjuvant setting. Anticancer Res 2013;33(4):1765-8.
Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 2004;22(16):3408-19. doi: 10.1200/JCO.2004.05.063.
