Phase I dose-escalating study of TAS-106 in combination with carboplatin in patients with solid tumors.

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.

• Authors: Aung Naing, Siqing Fu, Ralph G Zinner, Jennifer J Wheler, David S Hong, Kazuhito Arakawa, Gerald S Falchook, Razelle Kurzrock
• Journal: Investigational new drugs (Invest New Drugs) Vol. 32 Issue 1 Pg. 154-9 (Feb 2014) ISSN: 1573-0646 [Electronic] United States
• PMID: 23609829 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(3-C-ethynylribopentofuranosyl)cytosine
• Cytidine
• Carboplatin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Carboplatin (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Cytidine (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)
• Demography
• Dose-Response Relationship, Drug
• Female
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasms (drug therapy, metabolism, pathology)
• Nervous System (pathology)
• Young Adult