Faculty Collaboration Database

Phase I dose-escalating study of TAS-106 in combination with carboplatin in patients with solid tumors. Invest New Drugs 2014 Feb;32(1):154-9

Date

04/24/2013

Pubmed ID

23609829

Pubmed Central ID

PMC3913855

DOI

10.1007/s10637-013-9964-5

Scopus ID

2-s2.0-84899058447 (requires institutional sign-in at Scopus site)   7 Citations

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.

Author List

Naing A, Fu S, Zinner RG, Wheler JJ, Hong DS, Arakawa K, Falchook GS, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Carboplatin
Cytidine
Demography
Dose-Response Relationship, Drug
Female
Humans
Male
Maximum Tolerated Dose
Middle Aged
Neoplasms
Nervous System
Young Adult