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

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.

Non-metabolic role of UCK2 links EGFR-AKT pathway activation to metastasis enhancement in hepatocellular carcinoma

“…These findings suggest that UCK2 may have divergent pro-tumor functions either dependent or independent on its catalytic activity. This may partially explain the failure of a clinical trial of nucleoside 3′-C-ethynylcytidine (TAS-106), a cytidine analogue subjected to UCK2 phosphorylation, in treatment of head and neck cancer and nasopharyngeal cancer 36 .…”

Metronomic oral cyclosphosphamide as third-line systemic treatment or beyond in patients with inoperable locoregionally advanced recurrent or metastatic nasopharyngeal carcinoma

“…For chemo-naïve patients, monotherapy may be only recommended for those patients with suboptimal PS as the response rate and survival outcomes are less than satisfactory (Supplementary Table 2). [ 11 – 23 ] Platinum doublet chemotherapy is still recommended as the first-line treatment for those who have satisfactory PS, owing to the platinum sensitivity and long-standing history in clinical use (Supplementary Table 3). [ 12 , 24 – 52 ] In particular, cisplatin and 5-fluorouracil is the most popular selection due to its widespread use in head and neck squamous cell carcinoma and acceptable toxicity.…”

The conjugated antimetabolite 5-FdU-ECyd and its cellular and molecular effects on platinum-sensitive vs. -resistant ovarian cancer cellsin vitro

“…We conclude that 5-FdU-ECyd is more potent than cisplatin and can potentially act as single regime with lower side effects, especially in case of platinum-resistance, rather than a combinational partner within a polychemotherapeutic schedule. This is an important aspect as the monotherapeutic ECyd caused critical side effects in clinical studies [ 25 , 26 ].…”