Severe hematuria in a patient receiving bevacizumab and pembrolizumab for metastatic cervical cancer: a case report.

backgroundBevacizumab is a monoclonal antibody drug targeting Vascular Endothelial Growth Factor (VEGF), which binds to VEGF receptors to inhibit vascular endothelial cell proliferation and angiogenesis, thus inhibiting tumorigenesis. Pembrolizumab is a monoclonal antibody that can bind to the programmed death-1 (PD-1) receptor, which can block the binding of the PD-1 receptor to its ligands PD-L1 and PD-L2, and release PD-1 pathway-mediated suppression of immune responses. By blocking the activity of PD-1, the purpose of inhibiting tumor growth is achieved. CASE PRESENTATION: We report a severe hematuria of bevacizumab plus pembrolizumab, in a 58-year-old woman with metastatic cervical cancer. After three cycles every three weeks of consolidation chemotherapy (carboplatin, paclitaxel, bevacizumab) and following three cycles consolidation chemotherapy (carboplatin, paclitaxel, bevacizumab, pembrolizumab), the patient presented a worsening state. Manifested as massive gross hematuria with blood clots. After stopping chemotherapy, cefoxitin, tranexamic acid and hemocoagulase atrox therapy was administered resulting in rapid clinical improvement. The patient was a cervical cancer with bladder metastasis that increases the risk of development of hematuria. Inhibition of VEGF, which has anti-apoptotic, anti-inflammatory, and pro-survival influences on endothelial cells, weakens their regenerative capacity and increases expression of proinflammatory genes leading to weakened supporting layers of blood vessels and, hence, to damaged vascular integrity. In our patient, the development of hematuria may result from the anti-VEGF effect of bevacizumab. In addition, pembrolizumab may also cause bleeding, and the mechanism of bleeding caused by pembrolizumab is currently unclear, which may be related to immune mediation.

conclusionTo our knowledge, this is the first case reporting on the development of severe hematuria during bevacizumab plus pembrolizumab treatment, which should alert the clinicians in case of bleeding adverse events onset in older patients under bevacizumab plus pembrolizumab therapy.