Phase II study of TAS‐106 in patients with platinum‐failure recurrent or metastatic head and neck cancer and nasopharyngeal cancer

Cancer Medicine

Anne Tsao⁴  Edwin Pun Hui²  Rosalyn Juergens¹  Shanthi Marur¹  Tan Eng Huat⁵  Goh Boon Cher⁶  Ruey-Long Hong³  Waun Ki Hong⁴ 

[1] Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland;Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong;National Taiwan University Hospital, Taipei, Taiwan;Department of Thoracic and Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas;National Cancer Center Singapore, Singapore;National University of Singapore Hospital, Singapore

关键词: Head and neck squamous cell carcinoma;    nasopharyngeal cancer;    TAS‐106;   

DOI  :  10.1002/cam4.79

来源: Wiley

【 摘 要 】

Abstract

TAS-106, a RNA polymerase inhibitor, was studied in solid tumors with potential clinical benefit and reasonable tolerability. We conducted a multicenter, international phase II trial of TAS-106 in salvage metastatic or recurrent head and neck squamous cell cancer (HNSCC) and nasopharyngeal cancer (NPC) patients. TAS-106 monotherapy was given at 6.5 mg/m² over 24-h continuous infusion every 3 weeks. Translational studies for blood and tissue were included. Twenty-seven enrolled patients experienced the most common drug-related adverse events of neutropenia, fatigue, non-neutropenic fever, injection site reaction, and skin rash/dermatitis. The greater than or equal to grade 3 adverse events included neutropenia (14.8%), febrile neutropenia (7.4%), pneumonia (7.4%), and peripheral neuropathy (3.7%). The overall response rate was 0% in both subgroups; five HNSCC patients had stable disease (median duration 99 days) and four NPC patients had stable disease (median duration of 92.5 days). Median progression-free survival (PFS) for HNSCC patients was 52 days (95% CI 43.0–99.0 days) and 48 days (95% CI 41.0–83.0 days) for NPC. Median overall survival (OS) for HNSCC patients was 175 days (95% CI 92.0–234.0 days) and 280 days (95% CI 107.0–462.0 days) for NPC. The TAS-106 plasma levels were equivalent between Asian and Caucasian patients. There was no significant correlation of tumor UCK2 protein expression levels to TAS-106 efficacy. TAS-106 was reasonably tolerated in patients with platinum-failure HNSCC and NPC. The administration schedule of 24-h continuous infusion prevented neurologic toxicity, but had myelosuppression as its main toxicity. There was no anti-tumor efficacy seen with TAS-106 monotherapy. Future studies will focus on TAS-106 combinations and mechanisms of drug resistance.

【 授权许可】

CC BY   
© 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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