In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e18052-e18052
Abstract:
e18052 Background: Efatutazone is a novel, third-generation thiazolidinedione (TZD) showing higher potency over second generation TZDs, such as pioglitazone. In non-Asian patients with advanced solid tumors, the recommended dose is 0.50 mg twice-daily (BID) in accordance with PK, PD and safety analyses in a US phase 1 study. This study assessed the safety, tolerability, PK, antitumor activity, PD, and determined the recommended dose of efatutazone in combination with erlotinib in Korean patients. Methods: This was an open-label, dose-escalation study using a 3+3 design in combination with erlotinib. Each patient participated in only 1 dose group and received oral efatutazone 0.25 or 0.50 mg BID with administration of erlotinib 150 mg QD. After determining the recommended dose of efatutazone, 9 additional patients were enrolled to the recommended dose for further assessment. PK samples were collected at day 1 and 22. PD samples were collected weekly until day 36. All subjects provided written informed consent. Results: A total of 14 patients were enrolled (10 male and 4 female; age range: 39–73 years; 12 Adenocarcinoma and 2 Squamous cell carcinoma; EGFR mutation: 5 positive, 4 negative and 5 not conducted) and received treatment at doses of 0.25 and 0.50 mg BID (n= 3 in 0.25mg, n= 11 in 0.50mg cohort). DLT were not observed, and the MTD was not reached. Efatutazone was well tolerated. The majority of patients experienced edema (78.6%, 11 out of 14 patients) and weight increase (64.3%, 9 out of 14 patients), often requiring diuretics. Five out of 14 patients showed PR (3 confirmed in 0.50mg cohort) and 4 patients showed SD. Efatutazone increased plasma adiponectin levels in a dose-dependent manner. Conclusions: Efatutazone is a novel anticancer therapy and in combination with erlotinib was tolerated and demonstrated early evidence of antitumor activity. Although the MTD for efatutazone was not reached, 0.50 mg BID, corresponding to the global recommended dose, was selected as the recommended dose for Korean patients. Full safety data and clinical activity data will be presented.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.e18052
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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