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 IgG 1. 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(mC RC). 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 mostcommon 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 mC RC, and will provide recommendations for toxicity management. 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 IgG 1. 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 (mC RC). 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. 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 This review will address the toxicities noted in trials using Ziv for the treatment of mC RC, and will provide recommendations for toxicity management.