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World J Clin Oncol. Dec 10, 2014; 5(5): 1028-1035
Published online Dec 10, 2014. doi: 10.5306/wjco.v5.i5.1028
Incidence and management of ZIv-aflibercept related toxicities in colorectal cancer
Muhammad Wasif Saif, Valerie Relias, Kostas Syrigos, Krishna S Gunturu
Muhammad Wasif Saif, Valerie Relias, GI Oncology Exp. Therapeutic, Tufts Medical Center-Tufts Cancer Center, Boston, MA 02111, United States
Kostas Syrigos, Oncology Unit, Third Department of Medicine, Athens Medical School, Sotiria General Hospital, Athens, Greece
Krishna S Gunturu, Lahey Clinic, Burlington, MA 02111, United States
Author contributions: Saif MW, Gunturu KS and Relias V contributed to collection of data and writing the manuscript; and Syrigos K reviewed and agreed with the manuscript.
Correspondence to: Muhammad Wasif Saif, MD, MBBS, Professor of Medicine, Tufts School of Medicine, Director, GI Onc. Program & Program leader, GI Oncology Exp. Therapeutic, Tufts Medical Center-Tufts Cancer Center, 800 Washington Street, 7-South, Suit: 7099, Boston, MA 02111, United States. wsaif@tuftsmedicalcenter.org
Telephone: +1-617-6368077 Fax: +1-617-6367060
Received: January 10, 2014
Revised: May 12, 2014
Accepted: May 29, 2014
Published online: December 10, 2014
Processing time: 335 Days and 11.7 Hours
Abstract

Ziv-afilbercept (Zaltrap, Ziv) is a humanized fusion protein constructed by joining the vascular endothelial growth factor (VEGF) binding portions of human VEGF receptors 1 and 2 to the Fc portion of human immunoglobulin IgG1. Recently, a randomized, open-label, phase III study compared 5-fluorouracil, leucovorin, irinotecan (FOLFIRI)/Ziv with FOLFIRI/placebo in patients who had been previously treated with oxaliplatin based chemotherapy for metastatic colon cancer (mCRC). Patients who had received prior bevacizumab therapy were also eligible. This study showed that the addition of Ziv improved overall survival with median survival time of 13.5 mo vs 12.06 mo in ziv vs placebo arm. Ziv also improved progression free survival from 4.67 mo to 6.9 mo with a response rate of 19.8% in the Ziv/FOLFIRI group vs 11.1% in FOLFIRI alone group. This led to the approval of Ziv in combination with FOLFIRI in metastatic colon cancer patients treated with prior oxaliplatin regimens. The most common side effects were diarrhea, stomatitis, fatigue, hypertension, weight loss, loss of appetite, abdominal pain, and headache. As the use of Ziv has become more widespread in oncology practices, familiarity with the toxicity profile of the drug and the use of practice guidelines for their treatment has become increasing important. This review will address the toxicities noted in trials using Ziv for the treatment of mCRC, and will provide recommendations for toxicity management.

Keywords: Ziv-aflibercept; Colon cancer; Metastatic; Bleeding; Hypertension

Core tip: Ziv is an anti-angiogenic agent which has shown survival benefit in colorectal cancer. Side effects of this drug include hypertension, bleeding, perforation and delayed wound healing among others. In this paper, we review the side effects of Ziv and discuss how to manage those toxicities.