贝伐单抗能增加癌症患者的重症蛋白尿风险

专家评价：

Michael Mayr and
Jurg Schifferli
Medizinische Universitaetsklinik Basel, Switzerland
Nephrology

In this study, the authors not only confirm that the vascular endothelial growth factor (VEGF)-neutralizing antibody bevacizumab (avastin) can cause proteinuria but also point out its role as a risk factor for severe proteinuria in cancer patients. Interestingly, there seems to be a dose-dependent effect whereby patients treated for renal cell carcinoma (RCC) are at highest risk of developing severe proteinuria.

VEGF plays an important role in tumor angiogenesis, growth, progression, invasion and metastasis. This led to the development and successful introduction of a new class of drugs in cancer therapy that are characterized by inhibiting VEGF signaling pathways at different levels. In the current meta-analysis of 16 randomized controlled trials, 6482 patients treated with bevacizumab in combination with chemotherapy were compared to 5786 patients treated with chemotherapy alone. The patients suffered either from colorectal cancer, non-small cell lung cancer, breast cancer, pancreatic cancer, renal cell carcinoma or malignant mesothelioma. The summary incidence rate of high-grade proteinuria in patients treated with bevacizumab was 2.2%, whereby the addition of bevacizumab increased the risk of severe proteinuria and nephrotic syndrome by a factor of 5 and 8, respectively. Furthermore and clinically important, patients suffering from RCC had the highest risk for severe proteinuria with an incidence rate of 12%. When low versus high bevacizumab dosages were compared (arbitrarily determined as a weekly dosage of 2.5mg/kg compared to 5mg/kg), a dose-dependent effect on the development of severe proteinuria could be observed. At the moment, it is unclear whether the development of severe proteinuria has any impact on the clinical outcome of cancer patients. At least at the study level, no correlation between high-grade proteinuria and progression-free survival or overall survival could be found. However, this does not exclude clinically relevant implications at the patient level. Therefore, patients treated with bevacizumab and, assuming a class effect, other VEGF signaling pathway inhibitors, such as axitinib, VEGF Trap, sorafenib, and sunitinib, should be closely monitored to prevent undesired renal and cardiovascular side effects. Finally, the degree of proteinuria in relation to the tumor type needs further exploration. It is unclear whether the effect seen in patients with RCC is simply explainable by secondary effects due to the loss of renal mass since almost all patients are nephrectomised?