De-escalation treatment of human papillomavirus-positive oropharyngeal squamous cell carcinoma: an evidence-based review for the locally advanced disease.

PURPOSE OF REVIEW: Oropharyngeal cancer (OPC) incidence is increasing worldwide, especially in developed countries where it seems to be etiologically related to the elevating rates of high-risk human papillomavirus (HPV) infection. Considered a distinct disease because of its weak correlation with the traditional risk factors (tobacco use and alcohol), it has different patterns of survival outcomes, locoregional and distant failure, generally with better prognosis independently of the treatment. The standard therapeutic approach for locally advanced (LA) OPCs includes radiation therapy with concurrent chemotherapy, resulting in severe toxicities with negative impacts in quality of life (QoL). Considering this, efforts emerged to de-intensify treatment modalities in selected patients and achieve less morbidity while maintaining the favorable outcome. RECENT FINDINGS: Several de-escalated treatment strategies for HPV-related OPCs have been proposed to date with some of them being assessed in ongoing clinical trials. The main approaches encompass: minimally invasive surgery and reduced adjuvant treatment; antiepidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) as alternative to chemotherapy concurrent with radiation therapy; adjusted radiation therapy dose intensity in responders to induction chemotherapy; reduced-dose radiation therapy. SUMMARY: There is still a lack of evidence to support de-intensification treatment for HPV-positive LA-OPC in clinical practice, and it remains investigational. Ongoing trials based on risk stratification might identify subgroups with greatest benefits of de-escalation strategies, reducing treatment morbidity without constituting the favorable prognosis.

Analysis of Efficacy and Toxicity Profile of First-Line Sunitinib or Pazopanib in Metastatic Clear Cell Renal Cell Carcinoma in the Brazilian Population.

Purpose Sunitinib and pazopanib are multitargeted tyrosine kinase inhibitors (TKIs) that act against vascular endothelial growth factor receptors and are standard first-line treatment options for metastatic clear cell renal cell carcinoma (ccRCC). The Brazilian public health system diverges from the randomized clinical trials in the availability of first and subsequent lines of treatment and in clinical and demographic characteristics of patients. Therefore, it is essential to describe the history of advanced ccRCC during and after TKI treatment in this population. Methods We performed a retrospective analysis of patients with advanced ccRCC treated with a first-line TKI (either sunitinib or pazopanib) between February 2009 and March 2017 in a single academic Brazilian cancer center (Instituto do Câncer do Estado de São Paulo). Results Of the 222 patients, 109 were treated with sunitinib and 113 with pazopanib. The median duration of treatment and overall survival (OS) were 6.4 and 15.2 months for sunitinib and 6.7 and 14.2 months for pazopanib, respectively. Discontinuation of treatment occurred secondarily to progressive disease or death in 64.2% of patients using sunitinib and in 54.8% of patients using pazopanib. Adverse events were responsible for discontinuation of treatment in 28.4% of patients in the sunitinib group and in 22.1% in the pazopanib group. According to Memorial Sloan-Kettering Cancer Center risk categories, the OS was 32.9 months, 15.9 months, and 8.1 months for low risk, intermediate risk, and poor risk, respectively (hazard ratio, 1.72; 95% CI, 1.13 to 2.26; P < .001). Conclusion The use of TKI inhibitors as first-line treatment of metastatic RCC is effective and feasible in the Brazilian public health. However, the median OS of our population is considerably lower compared with the prospective trials that evaluated the same drugs.