Adverse Effects of Chemotherapy Regimens Used in Colorectal Cancer Patients in a Referral Cancer Center in North of Iran, 2008-2014

  • Ebrahim Salehifar Board certified Clinical PharmacistGastrointestinal Research Center Mazandaran University of Medical Sciences, Sari, Iran
  • Shayesteh Gheibi Resident of Clinical Pharmacy, Pharmaceutical Research Center, Mazandaran University of Medical Sciences, Sari, Iran
  • Ghasem Janbabaei Board certified Hematologist Oncologist, Gastrointestinal Research Center, Mazandaran University of Medical Sciences, Sari, Iran
  • Khali Mousavi Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Keywords: ADR, FOLFOX, XELOX, neuropathy, mucositis

Abstract

Introduction: Gastrointestinal tract cancers are the most common cancers in Iran with a growing incidence in the past two decades, especially in the Northern provinces of the country. Different chemotherapy regimens have been used in the treatment of colorectal cancers (CRC). Considering lack of data, this study aimed to determine the adverse drug reactions (ADRs) of chemotherapy regimens used in treatment of patients with CRC.Material and methods:This cross-sectional prospective study was carried out in Emam Khomeini Hospital and Tooba Clinic, both affiliated to Mazandaran University of Medical Sciences. ADRsof chemotherapy regimens including nausea, vomiting, fever and neutropenia, diarrhea, oral mucositis, neuropathy and hair loss were documented based on CTCAE Version 4.0 (Common Terminology Criteria for Adverse Events).Results:Two hundred sixty seven different courses of chemotherapy regimens received by 48 patients were evaluated in terms of adverse events. Three more common chemotherapy regimens wereFOLFOX (Folinic acid, Fluorouracil, Oxaliplatin), FOLFIRI (Folinic acid, Fluorouracil, Irinotecan) and XELOX (Capecitabine, Oxaliplatin).FOLFIRI and FOLFOX regimens were associated with more nausea and vomiting compared to XELOX. The rate of vomiting was marginally different between regimens (P=0.06). Most of nausea and all vomiting were as grade 1 or 2. The diarrhea was more common with FOLFOX (P=0.027). Whereas 14% of patients received FOLFIRI experienced neutropenia, none of patients in XELOX and almost 5% of FOLFOX patients experienced neutropenia. Mucositis happened in 16.1 and 17.8% of patients received FOLFOX and XELOX, respectively. The rate of neuropathy was different among regimens, as XELOX and FOLFOX were associated with more neuropathy compared with FOLFIRI (P=0.019). The rate of hair loss and headache were not different between three regimens.Most of the side effects (e.g., nausea, neuropathy, and headache) were acute. Vomiting and mucositis with XELOX occurred after 24 hours of initiation of chemotherapy.Conclusion:The results of our study showed that the GI adverse events including nausea, vomiting and severe diarrhea were more common with FOLFIRI regimen. Mucositis and neuropathy were more common with XELOX. Hair loss was more common with FOLFIRI followed by XELOX and FOLFOX.  

References

Maindrault-Goebel F, Louvet C, Andre T, et al. Oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second- line therapy for metastatic colorectal cancer (FOLFOX6). Europ J Cancer 1999;35(9):1338-42.

Bouvier AM, Launoy G. Epidemiology of colorectal cancer. Rev Prat 2015;65(6):767-73.

Wadler S, Benson 3rd A, Engelking C, et al. Recommended guidelines for the treatment of chemotherapy-induced diarrhea. J Clin Oncol1998;16(9):3169-78.

Rothenberg ML, Eckardt JR, Kuhn JG, et al. Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. J Clin Oncol 1996;14(4):1128-35.

Benson III AB, Ajani JA, Catalano RB, et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol2004;22(14):2918-26.

Barbounis V, Koumakis G, Vassilomanolakis M, Demiri M, Efremidis AP. Control of irinotecan-induced diarrhea by octreotide after loperamide failure. Support Care Cancer 2001;9(4):258-60.

Wiela-Hojeńska A, Kowalska T, Filipczyk-Cisarż E, Łapiński Ł, Nartowski K. Evaluation of the Toxicity of Anticancer Chemotherapy in Patients with Colon Cancer. Adv Clin Exp Med 2015;24(1):103-11.

Cassidy J, Tabernero J, Twelves C, et al. XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol 2004;22(11):2084-91.

Andre T, Louvet C, Maindrault-Goebel F, et al. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous- infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. Europ J Cancer 1999;35(9):1343-7.

Skof E, Rebersek M, Hlebanja Z, Ocvirk J. Capecitabine plus Irinotecan (XELIRI regimen) compared to 5-FU/LV plus Irinotecan (FOLFIRI regimen) as neoadjuvant treatment for patients with unresectable liver-only metastases of metastatic colorectal cancer: a randomised prospective phase II trial. BMC Cancer 2009;9(1):120.

Broussard EK, Disis ML. TNM staging in colorectal cancer: T is for T cell and M is for memory. J Clin Oncol 2011;29(6):601-3.

Health UDo, Services H. Common terminology criteria for adverse events (CTCAE) version 4.0. National Cancer Institute. 2009 (09-5410).

Benson AB, Ajani JA, Catalano RB, et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 2004;22(14):2918-26.

Rothenberg ML, Eckardt JR, Kuhn JG, et al. Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. J Clin Oncol 1996;14(4):1128-35.

Wadler S, Benson A, Engelking C, et al. Recommended guidelines for the treatment of chemotherapy-induced diarrhea. J Clin Oncol 1998;16(9):3169-78.

Cassidy J, Clarke S, Díaz-Rubio E, 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;26(12):2006-12.

Chu E, DeVita Jr VT. Physicians’ Cancer Chemotherapy Drug Manual 2016: Jones & Bartlett Publishers; 2015.

Meyerhardt JA, Stuart K, Fuchs CS, et al. Phase II study of FOLFOX, bevacizumab and erlotinib as first-line therapy for patients with metastatic colorectal cancer. Ann Oncol 2007;18(7):1185-9.

Hurwitz H, Mitchell EP, Cartwright T, et al. A randomized, phase II trial of standard triweekly compared with dose-dense biweekly capecitabine plus oxaliplatin plus bevacizumab as first-line treatment for metastatic colorectal cancer: XELOX-A-DVS (dense versus standard). Oncologist 2012;17(7):937-46

Hasegawa J, Nishimura J, Mizushima T, et al. Neoadjuvant capecitabine and oxaliplatin (XELOX) combined with bevacizumab for high-risk localized rectal cancer. Cancer Chemother Pharmacol 2014;73(5):1079-87.

Published
2017-09-18
How to Cite
1.
Salehifar E, Gheibi S, Janbabaei G, Mousavi K. Adverse Effects of Chemotherapy Regimens Used in Colorectal Cancer Patients in a Referral Cancer Center in North of Iran, 2008-2014. jpc. 4(1-2):9-3.
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Original Article(s)