Phase I dose-escalating study of TAS-106 in combination with carboplatin in patients with solid tumorsReport as inadecuate

Phase I dose-escalating study of TAS-106 in combination with carboplatin in patients with solid tumors - Download this document for free, or read online. Document in PDF available to download.

Investigational New Drugs

, Volume 32, Issue 1, pp 154–159

First Online: 23 April 2013Received: 19 February 2013Accepted: 26 March 2013DOI: 10.1007-s10637-013-9964-5

Cite this article as: Naing, A., Fu, S., Zinner, R.G. et al. Invest New Drugs 2014 32: 154. doi:10.1007-s10637-013-9964-5 Summary

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 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.

KeywordsPhase I Platinum Ovarian Non-small-cell lung cancer TAS-106 Resistance Presented in part at Japanese Society of Medical Oncology at Osaka, Japan in July 2012.

Sponsored research agreementTaiho Pharmaceuticals, Inc.

Download fulltext PDF

Author: Aung Naing - Siqing Fu - Ralph G. Zinner - Jennifer J. Wheler - David S. Hong - Kazuhito Arakawa - Gerald S. Falchook -


Related documents