Abstract
BACKGROUND: TAS-106 was designed to inhibit RNA synthesis by blocking RNA polymerases I, II, and III. METHODS: This was a single-center, open-label, phase I study to identify the maximum tolerated dose (MTD), pharmacokinetics, and biologic effects of the combination of TAS-106 and carboplatin, following a standard 3 + 3 design. This phase I trial was comprised of a regimen of a 60-min IV infusion of carboplatin on day 1 of each 21-day cycle followed by a 24-h infusion of TAS-106, also on day 1 of each cycle. RESULTS: 39 patients were treated (21 male, 18 female, median age 62 years, range 21-80 years). Median number of prior therapies was 4. Maximum Tolerated Dose (MTD) was 3 mg/m(2) TAS-106 with AU 4 carboplatin. Dose-limiting toxicities were neutropenia and thrombocytopenia, with and without growth factor support. While no patients achieved a complete or partial response, four patients had stable disease lasting ≥4 months, including one patient each with ovarian, non-small cell lung, basal cell and colorectal cancer. CONCLUSIONS: In summary, the combination of TAS-106 and carboplatin was well-tolerated, and further studies in non-small cell lung and ovarian cancer are warranted to assess the efficacy of this drug combination.