Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Phase 1b study of lenvatinib (E7080) in combination with temozolomide for treatment of advanced melanoma. Oncotarget 2015 Dec 15;6(40):43127-34

Date

10/28/2015

Pubmed ID

26503473

Pubmed Central ID

PMC4767496

DOI

10.18632/oncotarget.5756

Scopus ID

2-s2.0-84952360368 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

OBJECTIVE AND METHODS: In this phase 1b study, patients with stage 4 or unresectable stage 3 melanoma were treated with escalating doses of lenvatinib (once daily) and temozolomide (TMZ) (days 1-5) in 28-day cycles, to determine the maximum tolerated dose (MTD) of the combination. Dose Level (DL)1: lenvatinib 20 mg, TMZ 100 mg/m2; DL2: lenvatinib 24 mg, TMZ 100 mg/m2; DL3: lenvatinib 24 mg, TMZ 150 mg/m2. Adverse events (AEs) were recorded and tumor response assessed per RECIST 1.0.

RESULTS: Dose-limiting toxicity occurred in 1 of 32 treated patients (DL1); MTD was not reached. The highest dose administered was lenvatinib 24 mg + TMZ 150 mg/m2. Most common treatment-related AEs included fatigue (56.3%), hypertension (53.1%), and proteinuria (46.9%). Overall objective response rate was 18.8% (6 patients), all partial response; (DL1, n = 1; DL3, n = 5). Stable disease (SD) ≥ 16 weeks was observed in 28.1% of patients (DL1 and DL2, n = 1 each; DL3, n = 7); 12.5% of patients had SD ≥ 23 weeks. Single and repeat-dose pharmacokinetics of lenvatinib were comparable across cycles and with concomitant TMZ administration.

CONCLUSIONS: Lenvatinib 24 mg/day + TMZ 150 mg/m2/day (days 1-5) demonstrated modest clinical activity, an acceptable safety profile, and was administered without worsening of either lenvatinib- or TMZ-related toxicities in this patient group.

Author List

Hong DS, Kurzrock R, Falchook GS, Andresen C, Kwak J, Ren M, Xu L, George GC, Kim KB, Nguyen LM, O'Brien JP, Nemunaitis J

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Dacarbazine
Dose-Response Relationship, Drug
Female
Humans
Male
Maximum Tolerated Dose
Melanoma
Middle Aged
Phenylurea Compounds
Quinolines
Young Adult