Gastrointestinal Adverse Effects in Advanced Colorectal Carcinoma Patients Treated with Different Schedules of FOLFOX

  • Bano, Nusrat (Pharmacology Department, Ziauddin University) ;
  • Najam, Rahila (Pharmacology Department, University of Karachi) ;
  • Qazi, Faaiza (Jinnah University for Women) ;
  • Mateen, Ahmed (Radiotherapy Department, Karachi Institute of Radiotherapy and Nuclear Medicine)
  • Published : 2014.10.23


Background: To assess the frequency and severity of gastrointestinal adverse effects in advanced colorectal carcinoma patients treated with four different schedules of FOLFOX. Materials and Methods: Patients (median age 61 years) who underwent surgery were included in the study. All had measureable disease at CT scan, ultrasonography or clinical examination. Toxicity was graded on a scale of 1-5 according to the general grade definition of CTC v2.0. The severity of adverse effects (Grade 3 and 4) assessed in each treatment arm was compared. Results: Differences between the incidence rates of 3 and 4 toxicity and all grades of toxicity for all parameters in GI toxicity were very highly significant (p<0.001). Severe gastrointestinal symptoms of toxicity were noted with FOLFOX7 (oxaliplatin $130mg/m^2$). Grade 3 diarrhea was reported in 25% patients and grade 4 diarrhea in 4% in the FOLFOX7 treatment arm. Grade 2 vomiting was very frequently reported in the FOLFOX4 treatment arm (oxaliplatin $85mg/m^2$). Grade 2 stomatitis was reported in 42% patients treated with mFOLFOX6 (oxaliplatin $100mg/m^2$). Differences in the incidence rate of nausea, diarrhea and stomatitis among all treatment arms of FOLFOX were significant (p<0.05). Conclusions: Severe diarrhea is associated with FOLFOX7 treatment. No grade 3 or 4 GI toxicity was reported in patients of the mFOLFOX6 arm.


  1. Bano N, Rahila N, Mateen A (2013d). Comparative assessment of skin and subcutaneous toxicity in patients of advanced colorectal carcinoma treated with different schedules of FOLFOX. Asian Pac J Cancer Prev, 14, 1781-86.
  2. Bano N, Najam R, Mateen A (2013a). Neurological adverse effects in patients of advanced colorectal carcinoma treated with different schedules of FOLFOX. Chemother Res Pract, 2013, 379870.
  3. Bano N, Najam R (2013b). Oxaliplatin: Its use in advanced colorectal carcinoma. Chem Inform, 44.
  4. Bano N, Najam R, Mateen A, Mirza T (2013c). Effects on cardiac biomarkers in colorectal cancer patients treated with FOLFOX. Pak J Med Dent, 2, 9-15.
  5. Carlotto A, Hogsett VL, Maiorini EM, Razulis JG, Sonis ST (2013). The economic burden of toxicities associated with cancer treatment: review of the literature and analysis of nausea and vomiting, diarrhoea, oral mucositis and fatigue. PharmacoEconomics, 31, 753-66.
  6. Comeau JM, Mohundro BL (2013). From bench to bedside: Promising colon cancer clinical trials. Am J Manag Care, 19, 32-7.
  7. Dogan K, Oztop I, Yavuzsen T, Ellidokuz H, and Yilmaz H (2011). Evaluation of the efficacy of modified De Gramont and modified FOLFOX4 regimens for adjuvant therapy of locally advanced rectal cancer. Asian Pac J Cancer Prev, 12, 3181-86.
  8. Gibson RJ, Keefe DMK, Lalla RV, et al (2013). Systematic review of agents for the management of gastrointestinal mucositis in cancer patients. Support Care Cancer, 21, 313-26.
  9. Lee HJ, Kim HS, Park NH, et al (2013). Feasibility of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in heavily pretreated patients with recurrent epithelial ovarian cancer. Cancer Res Treat, 45, 40-7.
  10. Halit K, Deniz K, Berk V, Inanc M, Ozkan M (2012). Association of human epidermal growth factor receptor-2 expression and clinicopathological findings in patients with colorectal cancer. Asian Pac J Cancer Prev, 13, 6221-25.
  11. Joanne C, Tang V, Leung R, et al (2013). Efficacy and tolerability of adjuvant oral capecitabine plus intravenous oxaliplatin (XELOX) in Asian patients with colorectal cancer: 4-year analysis. Asian Pac J Cancer Prev, 14, 6585-90.
  12. Kuebler JP, Wieand HS, O'Connell MJ, et al (2007). Oxaliplatin combined with weekly bolus 5-fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP protocol C-07. J Clin Oncol, 25, 2198-204.
  13. Najam R, Bano N, Mateen A (2013). Comparative cardiac toxicity in two treatment schedules of 5-FU/LV for colorectal carcinoma. Pak J Pharm Sci, 26, 1013-22.
  14. Nakatsumi H, Komatsu Y, Yuki S, et al (2013). Optimal dose period for indisetron tablets for preventing chemotherapyinduced nausea and vomiting with modified FOLFOX6: A randomized pilot study. Chemother, 58, 439-44.
  15. Qi C, Xia HW, Ge XJ, et al (2013). Serum miR-19a predicts resistance to FOLFOX chemotherapy in advanced colorectal cancer cases. Asian Pac J Cancer Prev, 14, 7421-26.
  16. Ramanathan RK, Clark JW, Kemeny NE, et al (2003). Safety and toxicity analysis of oxaliplatin combined with fluorouracil or as a single agent in patients with previously treated advanced colorectal cancer. J Clin Oncol, 21, 2904-11.
  17. Schultheis B, Folprecht G, Kuhlmann J, et al (2013). Regorafenib in combination with FOLFOX or FOLFIRI as first-or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study. Ann Oncol, 24, 1560-67.
  18. Sharif S, O'Connell MJ, Yothers G, Lopa S, Wolmark N (2008). FOLFOX and FLOX regimens for the adjuvant treatment of resected stage II and III colon cancer. Cancer Invest, 26, 956-63.
  19. Uncu D, Aksoy S, Cetin B, et al (2013). Results of adjuvant FOLFOX regimens in stage III colorectal cancer patients: Retrospective analysis of 667 patients. Oncol, 84, 240-5.

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