Lenvatinib(E7080)这个药怎么样

costa_na · 发表于 2014-9-23 13:07:38

Phase I/II study of E7080 (lenvatinib), a multitargeted tyrosine kinase inhibitor, in patients (pts) with advanced hepatocellular carcinoma (HCC): Initial assessment of response rate.

Abstract:

Background: Lenvatinib is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT and PDGFRβ. Maximum tolerated dose (MTD) of lenvatinib for solid tumor pts was determined to be 25 mg once daily dosing (qd), and MTD for HCC pts with Child-Pugh A was determined to be 12 mg qd. A preliminary assessment of response rate is presented in this report.

Methods: Between July 9, 2010 and June 22, 2011, 46 pts with advanced HCC with Child-Pugh A were enrolled in Japan (n=43) and Korea (n=3). Pts may have received up to one prior treatment regimen including sorafenib. Pts were treated with a starting dose of lenvatinib 12 mg once daily in 28 day cycles until disease progression or development of unmanageable toxicities. Response rate was assessed by RECIST 1.1 (modified to evaluate viable lesions).

Results: The first 42 consecutively enrolled pts (med age: 67; M: 76%, F: 24%) were evaluable for response and form the basis of this report. 45% had extra hepatic spread, 24% received prior chemotherapy and 91% had prior locoregional therapy. 19% were withdrawn from therapy due to adverse event. The most common toxicities were hypertension 71% (Gr 3: 48%), anorexia 50% (Gr 3: 2.4%), proteinuria 45% (Gr 3: 14%), palmar-plantar erythrodysaesthesia syndrome 43% (Gr 3: 4.8%), fatigue 43% (Gr 3: 0%), and thrombocytopenia 33% (Gr 3: 19%). No pts experienced Gr 4 toxicity. Confirmed Partial Responses (PRs) were observed in 14 pts (RR: 33%, 95% CI: 20-50) based on investigator assessment. Updated efficacy including median Time to Progression and survival data will be reported.

Conclusions: Lenvatinib 12 mg qd when administered to advanced HCC pts with Child-Pugh A is associated with manageable toxicity. The preliminary assessment of efficacy on the basis of overall response rate suggests that lenvatinib may represent a new potential therapeutic agent for advanced HCC pts. Further assessment of safety and efficacy is ongoing.

source: http://meetinglibrary.asco.org/content/87667-115

从这个Ph1/2的临床来看，7080对肝细胞癌的剂量是每天12mg

costa_na · 发表于 2014-9-23 13:08:58

A Multicenter, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Versus Sorafenib in First-Line Treatment of Subjects With Unresectable Hepatocellular Carcinoma

Drug: E7080
Lenvatinib: 12 mg (or 8 mg) once daily (QD) oral dosing

source: http://clinicaltrials.gov/show/NCT01761266

每天12mg(可以减量到8mg)

小P · 发表于 2014-9-23 15:24:53

costa_na 发表于 2014-9-23 13:08
A Multicenter, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Ve ...

谢谢版主!我昨天打电话到安徽医大负责做这药临床的医生,她告诉我,这药目前在国内20家医院做临床,用量根据病人体重在8--12MG之间,至于用法--是否空腹、胃溶还是肠溶就不敢问了。

海云轩 · 发表于 2014-11-16 20:29:49

一起努力每一天发表于 2014-9-16 10:56
似乎不难搞到，但用量，用法现在还没弄清楚。准备下一步试这个药！

E7080您用上了吗？效果如果？用的剂量？我打算用，谢谢您！

lostm · 发表于 2014-11-21 15:57:19

这是asco2014上发布的研究计划。三期了。12mg每天

A multicenter, open-label, phase 3 trial to compare the efficacy and safety of lenvatinib (E7080) versus sorafenib in first-line treatment of subjects with unresectable hepatocellular carcinoma.

Subcategory:
Hepatobiliary Cancer
Category:
Gastrointestinal (Noncolorectal) Cancer
Meeting:
2014 ASCO Annual Meeting
Session Type and Session Title:
General Poster Session, Gastrointestinal (Noncolorectal) Cancer
Abstract Number:
TPS4153

Citation:
J Clin Oncol 32:5s, 2014 (suppl; abstr TPS4153)

Author(s):
Richard S. Finn, Ann-Lii Cheng, Kenji Ikeda, Masatoshi Kudo, Toshiyuki Tamai, Corina E. Dutcus, Steven Younger, Kwang-Hyub Han, Shukui Qin, Eric Raymond; Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Toranomon Hospital, Tokyo, Japan; Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan; Eisai, Tokyo, Japan; Eisai, Woodcliff Lake, NJ; Severance Hospital, Yonsei University, Seoul, South Korea; PLA Cancer Center of Nanjing Bayi Hospital, Nanjing, China; Hopital Saint-Antoine, Paris, France

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract:

Background: Lenvatinib (L, E7080) is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRβ, RET and KIT. Given the role of angiogenesis in hepatocellular carcinoma (HCC), a phase 1/2 open-label study evaluated the safety and efficacy of L in 46 patients with advanced disease and Childs-Pugh (CP) A liver function status (Kudo ILCA 2013). Patients were treated with a starting dose of L 12 mg qd (28-d cycles) until disease progression or development of unmanageable toxicities. Median time to progression (TTP) was 12.8 months (mo; 95% confidence interval [CI] 7.23–14.7) and median overall survival (OS) was 18.7 mo (95% CI 12.8–25.1). The most common adverse events were hypertension 76% (Gr3 54%), palmar-plantar erythrodysesthesia syndrome 61% (Gr3 7%), proteinuria 59% (Gr3 20%), anorexia 57% (Gr3 2%), thrombocytopenia 50% (Gr3 33%), and fatigue 48% (Gr3 0%). Overall response rate (ORR) was 37%; 45.7% had stable disease. Methods: Based on these phase 2 data, a global, randomized, open-label phase 3 trial was designed to determine if L is non-inferior or superior compared to sorafenib (S) in advanced HCC. Eligible patients (N=940) with Barcelona Clinic Liver Cancer Stage B or C HCC, CP A status, and ECOG 0-1 will be randomized 1:1 to either L 12 mg or 8 mg orally qd (based on body weight [BW]) or S 400 mg orally bid. Patients will be stratified by region; macroscopic portal vein invasion, extrahepatic spread, or both; ECOG-PS; and BW (<60 vs ≥60 kg). The primary endpoint is OS. Secondary endpoints include progression-free survival, TTP, ORR (modified RECIST criteria), safety and PK/PD. Given an estimated median OS for S of approximately 10 mo, a 2.5 mo improvement was derived to achieve a hazard ratio (HR) of 0.8. Statistical study power (using a non-inferiority test by the 95% CI lower-limit method on log HR for OS) was determined based on this HR and a non-inferiority margin of 1.08, corresponding to 60% retention of S effect vs placebo. Based on these assumptions, the study power to declare non-inferiority or superiority is approximately 97% and 82%, respectively. The overall false positive rate is 0.05 (2-sided). Clinical trial information: NCT01761266.