当前位置： SCI文献检索 > ANTI-CANCER DRUGS期刊下所有文献 > Phase I trial of belinostat with cisplatin and etoposide in advanced solid tumors, with a focus on neuroendocrine and small cell cancers of the lung.

Phase I trial of belinostat with cisplatin and etoposide in advanced solid tumors, with a focus on neuroendocrine and small cell cancers of the lung.

Abstract：

:The standard-of-care for advanced small cell lung cancer (SCLC) is chemotherapy with cisplatin+etoposide (C+E). Most patients have chemosensitive disease at the outset, but disease frequently relapses and limits survival. Efforts to improve therapeutic outcomes in SCLC and other neuroendocrine cancers have focused on epigenetic agents, including the histone deacetylase inhibitor belinostat. The primary objective was to determine the maximum tolerated dose of the combination of belinostat (B) with C+E. Belinostat was administered as a 48-h continuous intravenous infusion on days 1-2; cisplatin was administered as a 1-h intravenous infusion on day 2; and etoposide was administered as a 1-h intravenous infusion on days 2, 3, and 4. Twenty-eight patients were recruited in this single-center study. The maximum tolerated dose was belinostat 500 mg/m/24 h, cisplatin 60 mg/m, and etoposide 80 mg/m. The combination was safe, although some patients were more susceptible to adverse events. Hematologic toxicities were most commonly observed. Objective responses were observed in 11 (39%) of 28 patients and seven (47%) of 15 patients with neuroendocrine tumors (including SCLC). Patients carrying more than three copies of variant UGT1A1 (*28 and *60) had higher serum levels of belinostat because of slower clearance. DNA damage peaked at 36 h after the initiation of belinostat, as did global lysine acetylation, but returned to baseline 12 h after the end of infusion. The combination of B+C+E is safe and active in SCLC and other neuroendocrine cancers. Future phase II studies should consider genotyping patients for UGT1A1*28 and UGT1A1*60 and to identify patients at an increased risk of adverse events.

journal_name

Anticancer Drugs

journal_title

Anti-cancer drugs

authors

Balasubramaniam S,Redon CE,Peer CJ,Bryla C,Lee MJ,Trepel JB,Tomita Y,Rajan A,Giaccone G,Bonner WM,Figg WD,Fojo T,Piekarz RL,Bates SE

doi

10.1097/CAD.0000000000000596

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

457-465

issue

eissn

0959-4973

issn

1473-5741

journal_volume

pub_type

杂志文章

在线工具

Phase I trial of belinostat with cisplatin and etoposide in advanced solid tumors, with a focus on neuroendocrine and small cell cancers of the lung.