演題抄録

FACO International Workshop

開催概要
開催回
第53回・2015年・京都
 

Phase Ib dose-escalation study of Eribulin (Eri) in combination with Gemcitabine (GEM) in patients (pts) with metastatic breast cancer (MBC)

演題番号 : FWS11-5

[筆頭演者]
Kashiwaba Masahiro:1 
[共同演者]
Goto Risa:3、Kondo Naoto:2、Hattori Masaya:2、Iwata Hiroji:2

1:Dpt. of Surgery, Iwate Medical University、2:Dpt. of Breast Oncology, Aichi Cancer Center Hospital、3:Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital

 

Background: Eri is a non-taxane microtubule inhibitor that has been proved to prolong overall survival in pts with advanced and recurrent breast cancer. Eri plus GEM induced additive anti-tumor effect in preclinical studies. We therefore conducted a phase 1b trial of Eri and GEM in pts with MBC to determine the maximum tolerated dose (MTD), dose limited toxicity (DLT), recommended dose (RD) for tolerability and pharmacokinetic (PK) in Japanese population.
Methods: According to modified Fibonacci 3+3 dose escalation method, Level 0 (initial does) Eri 1.1mg/m2 + GEM 800mg/m2 on day1,8. Level 1: Eri 1.4mg/m2 + GEM 800mg/m2. Level 2: Eri 1.4mg/m2 + GEM 1,000mg/m2, Level 3: Eri 1.4mg/m2 + GEM 1,250mg/m2 were planned. Pts pretreated with anthracycline and taxane, untreated with Eri and GEM, and with only non-measurable disease were eligible. Adverse events (AEs) were assessed by CTCAE 4.0. DLT of cycle 1 and PK were measured in cycle 1.
Results: No DLT was observed in Level 0. A DLT (G3 stomatitis) was observed in fourth patient in Level 1 . Finally seven pts were enrolled in this study which was small number than we preplanned. Therefore, MTD was not determined because a number of preplanning enrollment was not reached. Toxicities were observed as below; Neutropenia in all pts (G1:1pts, G3:3pts, G4:3pts). No G3/4 hemoglobin decreased and thrombocytopenia, AST (G1:6pts, G2:1pt) and ALT elevation (G1:5pts, G2:2pts) ,non-hematological toxicities (Myalgia, anorexia, fatigue, nausea, vomiting, dysguisia) were mild (G1 and 2). Notably, the frequency of stomatitis was high (3pts) and was determined DLT by one G3. The PK data showed tolerable interaction in Eri and GEM combination with large difference among individual pts.
Conclusion: The combination therapy with Eri (1.1mg/m2) and GEM (800mg/m2) was safe and well tolerated in Japanese population. The phase II study will be planned by using this determined dose combination therapy for metastatic breast cancer pts.

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臓器別:乳腺

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