Phase 1b study of lenvatinib (E7080) in combination with temozolomide for treatment of advanced melanoma. Oncotarget 2015 Dec 15;6(40):43127-34
Date
10/28/2015Pubmed ID
26503473Pubmed Central ID
PMC4767496DOI
10.18632/oncotarget.5756Scopus ID
2-s2.0-84952360368 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
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 JAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
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