A Phase II Study of Pazopanib in Asian Patients with Recurrent/Metastatic Nasopharyngeal Carcinoma

Abstract

Purpose: Nasopharyngeal carcinoma is endemic in Asia and angiogenesis is important for growth and progression. We hypothesized that pazopanib would have antiangiogenic activity in nasopharyngeal carcinoma.Experimental Design: A single arm monotherapy study of pazopanib in patients with WHO type II/III nasopharyngeal carcinoma who had metastatic/recurrent disease and failed at least one line of chemotherapy. A Simon's optimal 2-stage design was used. Patients with Eastern Cooperative Oncology Group (ECOG) 0-2 and adequate organ function were treated with pazopanib 800 mg daily on a 21-day cycle. The primary endpoint was clinical benefit rate (CR/PR/SD) achieved after 12 weeks of treatment. Secondary endpoints included toxicity and progression-free survival. Exploratory studies of dynamiccontrast enhanced computed tomography (DCE-CT) paired with pharmacokinetics (PK) of pazopanib was done.Results: Thirty-three patients were accrued. Patients were ECOG 0-1 with median age of 50 years (range 36-68). There were 2 (6.1%) partial responses, 16 (48.5%) stable disease, 11 (33.3%) progressive disease, 4 (12.1%) were not evaluable for response. The clinical benefit rate was 54.5% (95% CI: 38.0-70.2). Ten patients (30.3%) received more than 6 cycles (4 months) of treatment and 7 (21.2%) had PR/SD that lasted at least 6 months. One patient each died from epistaxis and myocardial infarction. Common grade 3/4 toxicities included fatigue (15.2%), hand-foot syndrome (15.2%), anorexia (9.1%), diarrhea (6.1%), and vomiting (6.1%). Serial DCE-CT scans show significant reductions in tumor blood flow, permeability surface area product, and fractional intravascular blood volume.Conclusion: Pazopanib showed encouraging activity in heavily pretreated nasopharyngeal carcinoma with an acceptable toxicity profile.

Risks of Proteinuria Associated with Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis

“…According to the inclusion criteria of each trial, patients were required to have an adequate renal, hepatic and hematologic function. Underlying malignancies included breast cancer [49], renal cell carcinoma [39], [50]–[59], thyroid cancer [60]–[62], pancreatic cancer [63], [64], soft tissue sarcoma [65], [66], glioblastoma [67], [68], hepatocellular carcinoma [38], [69], small-cell lung cancer [70], ovarian cancer [71], nasopharyngeal carcinoma [72], non-small-cell lung cancer [73], malignant mesothelioma [74], alveolar soft part sarcoma [75] and colorectal cancer [76]–[79]. The median Jadad score of the fourteen randomized controlled trials was 3: five of them had Jadad scores of 5 which mentioned the concealment of allocation clearly in the randomization process, and provided the number of patients who withdrew from the trials.…”

Risk of venous thromboembolic events associated with VEGFR‐TKIs: A systematic review and meta‐analysis

“…These trials represented three studies with sorafenib, 21,31,32 three with sunitinib, 20,33,34 three with vandetanib [35][36][37] and five with pazopanib. 2,[38][39][40][41] The characteristics of each included trial were presented in Table 2. The most frequently reported VTEs were pulmonary embolism.…”

Recurrent Nasopharyngeal Carcinoma: A Clinical Dilemma and Challenge

“…The receptor tyrosine kinase inhibitors gefitinib and erlotinib were evaluated in rnpc [94][95][96] , but the objective responses were not satisfactory. In a phase ii study by Lim et al 97 of pazopanib-a small-molecule inhibitor of vegf, platelet-derived growth factor, and C-kit tyrosine kinases-in recurrent or metastatic npc, 6.1% patients achieved a partial response, and 48.5% experienced stable disease, with 1-year pfs and os rates of 13% and 44.4% respectively. Elser et al 98 treated recurrent or metastatic squamous cell carcinoma of the head and neck (n = 20) or npc (n = 7) with sorafenib, an inhibitor of serine and threonine kinases such as C-Raf and B-Raf, vegf, and platelet-derived growth factor.…”