Managing Toxicities Associated With Antiangiogenic Biologic Agents in Combination With Chemotherapy for Metastatic Colorectal Cancer

Abstract

Toxicities commonly associated with antiangiogenic agents include hypertension, proteinuria, wound-healing complications, bleeding or hemorrhage, thromboembolic events, hypersensitivity reactions, and gastrointestinal perforation; however, toxicities most often attributed to chemotherapy include nausea, vomiting, diarrhea, constipation, fatigue, neuropathy, mucositis, hand-foot syndrome, hypersensitivity reactions, and myelosuppression. Patients with metastatic colorectal cancer (mCRC) who receive an antiangiogenic agent in combination with chemotherapy may experience toxicities related to both chemotherapy and the antiangiogenic agent. If possible, evidence-based interventions should be used for the management of toxicities. Patient education about expected toxicities and optimal toxicity management can promote the optimal use of therapy to improve survival and quality of life. Oncology nurses are well positioned to educate patients and their families on anticipated treatment and management of side effects. This article summarizes the incidence of toxicities associated with the antiangiogenic biologic agents aflibercept and bevacizumab, in combination with chemotherapy for patients with mCRC, and provides strategies for managing these toxicities based on clinical practice guidelines.

Dopamine is a safe antiangiogenic drug which can also prevent 5-fluorouracil induced neutropenia

“…In addition, these drugs can also cause neutropenia and thrombocytopenia . On the contrary, our results demonstrate that the antiangiogenic dose of DA is devoid of serious toxicities usually observed with the use of anti‐VEGF agents in the clinics such as sunitinib …”

“…Myelosuppression and thrombocytopenia are common problems in cancer patients receiving antiangiogenic drugs . Drugs that inhibit the actions of VEGFA can cause myelosuppression and thrombocytopenia as VEGFRs expressed in hematopoietic cells play a role in myelopoiesis and thrombopoiesis . However, the degree of suppression varies between drugs, with some causing both thrombocytopenia and neutropenia .…”

“…Drugs that inhibit the actions of VEGFA can cause myelosuppression and thrombocytopenia as VEGFRs expressed in hematopoietic cells play a role in myelopoiesis and thrombopoiesis . However, the degree of suppression varies between drugs, with some causing both thrombocytopenia and neutropenia . We therefore determined the platelet (Fig.…”

Renal Toxicities of Targeted Therapies

“…If the level of proteinuria is ≥2 g/24 h, current FDA guidelines recommend that the anti-angiogenic agent be suspended until the return of urine protein level to baseline [30]. There have been a few anecdotal reports of continuing or re-introducing the agent, while treating aggressively with anti-hypertensive agents [31].…”

“…If proteinuria of grade 1+ is present on screening urine analysis, then urine protein excretion should be quantified using a spot urine albumin/creatinine ratio. Referral to a nephrologist is recommended for additional evaluation and for the treatment of chronic kidney disease, and the timing of referral should be individualized [24,30].…”