Efficacy, Safety, and Pharmacokinetics of Axitinib in Nasopharyngeal Carcinoma: A Preclinical and Phase II Correlative Study
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AbstractPurpose: 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.
Acceptance Date19/12/2017
All Author(s) ListEdwin P. Hui, Brigette B. Y. Ma, Herbert H. F. Loong, Frankie Mo, Leung Li, Ann D. King, Ki Wang, Anil T. Ahuja, Charles M. L. Chan, Connie W. C. Hui, Chi H. Wong, Anthony T. C. Chan
Journal nameClinical Cancer Research
Year2018
Month3
Day1
Volume Number24
Issue Number5
PublisherAmerican Association for Cancer Research
Place of PublicationUnited States
Pages1030 - 1037
ISSN1078-0432
LanguagesEnglish-United Kingdom

Last updated on 2020-16-09 at 00:36