Integration of Antiangiogenic Therapy with Cisplatin and Gemcitabine Chemotherapy in Patients with Nasopharyngeal Carcinoma

Abstract

Purpose: Induction cisplatin and gemcitabine chemotherapy is a standard treatment for locally advanced nasopharyngeal carcinoma (NPC). Inhibition of VEGF axis has been shown to promote maturation of microvasculature and improve perfusion. We conducted a four-arm study to assess the effect of two doses of either sunitinib or bevacizumab with chemotherapy in NPC.Patients and Methods: Patients with treatment-na€ ve locally advanced NPC were treated with three cycles of 3-weekly cisplatin and gemcitabine preceded by 1 week of anti-VEGF therapy for each cycle, followed by standard concurrent chemoradiation: arm A patients received 7 days of 12.5 mg/day sunitinib; arm B 7 days of 25 mg/day sunitinib; arm C bevacizumab 7.5 mg/kg infusion; arm D bevacizumab 2.5 mg/kg infusion. Patients with metastatic NPC were treated with up to six cycles of similar treatment without concurrent chemoradiation.Results: Complete metabolic response (mCR) by whole body 18 FDG PET was highest in arm C (significant difference in four groups Fisher exact test P ¼ 0.001; type 1 error ¼ 0.05), with 42% mCR (95% confidence interval, 18-67) and 3-year relapse-free survival of 88% in patients with locally advanced NPC. Significant increase in pericyte coverage signifying microvascular maturation and increased immune cell infiltration was observed in posttreatment tumor biopsies in Arm C. Myelosuppression was more profound in sunitinib containing arms, and tolerability was established in arm C where hypertension was the most significant toxicity.Conclusions: Bevacizumab 7.5 mg/kg with cisplatin and gemcitabine was well tolerated. Promising tumor response was observed and supported mechanistically by positive effects on tumor perfusion and immune cell trafficking into the tumor.

Expression and Biological Functions of EPC1 in Nasopharyngeal Carcinoma

“…14 Currently, the main molecularly targeted therapeutic drugs with proven efficacy in the treatment of NPC are epidermal growth factor receptor (OMIM: 131550) inhibitors and vascular endothelial growth factor inhibitors. 15,16 Previous studies have demonstrated the clinical efficacy and good safety of molecular targeted therapy in NPC. However, many studies are only in the preclinical or early research stage, 17 and more phase III clinical trials are needed.…”

Treatment of Recurrent Nasopharyngeal Carcinoma: A Sequential Challenge

“…Compared with chemotherapeutic agents, the use of targeted therapy and immunotherapy in recurrent NPC is relatively limited, and in most cases they are not used alone, but in combination with chemotherapeutic agents or radiotherapy to provide better benefits [ 115 , 116 , 117 , 118 , 119 ]. A clinical study published by Ng et al showed that weekly IMRT with docetaxel plus cetuximab was shown to be effective in advanced recurrent NPC compared to TPF-induced chemotherapy, with a 3-year progression-free survival rate of 35.7% [ 107 ].…”

Nasopharyngeal Carcinoma and Its Microenvironment: Past, Current, and Future Perspectives

“…The inhibition of angiogenesis could enhance the effectiveness of standard chemoradiotherapy against NPC. Combination of VEGF inhibitor bevacizumab with chemotherapy promoted microvasculature maturation, enhanced immune infiltration and exhibited promising tumor response ( 172 ). Combination therapy of apatinib with cisplatin showed a synergistic effect in inhibition of tumor growth, repression of VEGFR-2 expression and reduction in microvascular density in preclinical models ( 173 ).…”