Phase II study of TAS-106 in patients with platinum-failure recurrent or metastatic head and neck cancer and nasopharyngeal cancer.
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/m(2) 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.
Department of Thoracic and Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. astsao@mdanderson.org
Anne
A
Tsao
Edwin Pun
EP
Hui
Rosalyn
R
Juergens
Shanthi
S
Marur
Tan Eng
TE
Huat
Goh Boon
GB
Cher
Ruey-Long
RL
Hong
Waun Ki
WK
Hong
Anthony Tak-Cheung
AT
Chan
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002277:Carcinoma; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D003562:Cytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D016879:Salvage Therapy; D000077195:Squamous Cell Carcinoma of Head and Neck; D015996:Survival Rate
C103084:1-(3-C-ethynylribopentofuranosyl)cytosine; D000970:Antineoplastic Agents; D003562:Cytidine
Head and neck squamous cell carcinoma; TAS-106; nasopharyngeal cancer