Bevacizumab Demonstrates Prolonged Disease Stabilization in Patients with Heavily Pretreated Metastatic Renal Cell Carcinoma: A Case Series and Review of the Literature

Abstract

There are now a variety of therapies approved for the treatment of metastatic renal cell carcinoma (RCC). These include the immunotherapeutics, alfa-interferon, and interleukin-2, and agents that target the vascular endothelial growth factor receptor (VEGFR) via its tyrosine kinase, such as sorafenib, sunitinib, and pazopanib, or the mammalian target of rapamycin (mTOR), such as temsirolimus and everolimus. Bevacizumab, a monoclonal antibody directed against the ligand, VEGF, has shown activity against RCC as a single agent in patients who had failed prior cytokine therapy and as first line therapy in combination with interferon. The activity of bevacizumab in patients who had received and failed prior therapy has not been described. We report our experience in 4 patients with metastatic RCC who had failed prior cytokine, TKI, and mTOR inhibitors who were treated with bevacizumab as single agent therapy. These heavily pretreated patients sustained very prolonged periods of stable disease (median of 12 months) with very little toxicity and excellent quality of life. The activity of this agent in patients who had failed prior therapies directed against the VEGFR and mTOR suggests that therapy targeting the ligand, VEGF, is still a viable approach in these patients and deserves further study.

Delayed Diagnosis of Osteonecrosis of the Jaw (ONJ) Associated with Bevacizumab Therapy in Colorectal Cancer Patients: Report of Two Cases

“…Another issue is for what duration is the bevacizumab treatment needed to induce ONJ. There is a considerable variation in the timing of the onset of ONJ, which occurred at any time between one to 12 months after the start of bevacizumab in the reported ONJ cases not receiving bisphosphonates [ 9 , 10 , 11 , 12 , 13 , 14 , 16 , 17 , 18 , 19 , 20 ], with the significant exception of one case of ONJ diagnosed 10 months after the last bevacizumab administration, and about two years after the start of treatment [ 15 ].…”

“…ONJ occurrence related to bevacizumab treatment was first reported by Estilo et al in 2008 [ 9 ]. Since then, other cases have been described in cancer patients [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ], including colorectal cancer patients [ 19 , 20 ].…”

Osteonecrosis of jaw beyond antiresorptive (bone-targeted) agents: new horizons in oncology

“…[77] Some other published cases are notable: one pancreatic cancer patient showed ONJ during treatment with bevacizumab and sorafenib [78] and one renal cell cancer patient had received bevacizumab plus temsirolimus [79]; another renal cell cancer patient developed ONJ during bevacizumab treatment, after previous treatments with sunitinib and temsirolimus. [80] To note, one glioblastoma patient developed a severe complication after a single bevacizumab infusion [81]compatible with complicated ONJ. Besides case reports, few data are available about frequency of bevacizumabrelated ONJ.…”

Osteonecrosis of the Jaw in Patients With Metastatic Renal Cell Cancer Treated With Bisphosphonates and Targeted Agents: Results of an Italian Multicenter Study and Review of the Literature

“…[18][19][20][21][22][23][24][25][26][27][28][29][55][56][57][58][59][60][61][62] As a consequence, targeted agents with antiangiogenic properties are now ascribed as a possible risk factor for ONJ in cancer patients.…”

“…Since the introduction of these agents into the therapeutic armamentarium, an increasing number of ONJ cases have been reported in RCC patients who receive NBPs in association with targeted agents, [18][19][20][21][22][23][24][25][26] or even in patients who receive targeted agents alone, mainly sunitinib. [27][28][29] Thus, an interaction between NBPs and targeted agents toward an increased ONJ risk has been suggested.…”