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Clin Cancer Res. 2018 Mar 1;24(5):1030-1037. doi: 10.1158/1078-0432.CCR-17-1667. Epub 2018 Jan 4.

Efficacy, Safety, and Pharmacokinetics of Axitinib in Nasopharyngeal Carcinoma: A Preclinical and Phase II Correlative Study.

Author information

1
Comprehensive Cancer Trials Unit, Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
2
Cancer Drug Testing Unit, Partner State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
3
Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
4
Tumor Marker Laboratory, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
5
Comprehensive Cancer Trials Unit, Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. anthonytcchan@cuhk.edu.hk.

Abstract

Purpose: We hypothesized that axitinib is active with an improved safety profile in nasopharyngeal carcinoma (NPC).Experimental Design: We evaluated axitinib in preclinical models of NPC and studied its efficacy in a phase II clinical trial in recurrent or metastatic NPC patients who progressed after at least one line of prior platinum-based chemotherapy. We excluded patients with local recurrence or vascular invasion. Axitinib was started at 5 mg twice daily in continuous 4-week cycles. Primary endpoint was clinical benefit rate (CBR), defined as the percentage of patients achieving complete response, partial response, or stable disease by RECIST criteria for more than 3 months.Results: We recruited 40 patients, who received a median of 3 lines of prior chemotherapy. Axitinib was administered for a mean of 5.6 cycles, with 16 patients (40%) receiving ≥6 cycles. Of 37 patients evaluable for response, CBR was 78.4% (95% CI, 65.6%-91.2%) at 3 months and 43.2% (30.4%-56.1%) at 6 months. Grade 3/4 toxicities were uncommon, including hypertension (8%), diarrhea (5%), weight loss (5%), and pain (5%). All hemorrhagic events were grade 1 (15%) or grade 2 (3%). Elevated diastolic blood pressure during the first 3 months of axitinib treatment was significantly associated with improved overall survival (HR, 0.29; 95% CI, 0.13-0.64, P = 0.0012). Patient-reported fatigue symptom was associated with hypothyroidism (P = 0.039). Axitinib PK parameters (Cmax and AUC(0-t)) were significantly correlated with tumor response, toxicity, and serum thyroid-stimulating hormone changes.Conclusions: Axitinib achieved durable disease control with a favorable safety profile in heavily pretreated NPC patients. Clin Cancer Res; 24(5); 1030-7. ©2018 AACR.

PMID:
29301831
DOI:
10.1158/1078-0432.CCR-17-1667
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