A phase I study of E7080, a multitargeted tyrosine kinase inhibitor, in patients with advanced solid tumours.
The objectives of this phase I study were to assess the safety and tolerability of E7080 in patients with advanced, refractory solid tumours; to determine the maximum tolerated dose (MTD) and pharmacokinetics profile of E7080; and to explore preliminary evidence of its anti-tumour efficacy.
E7080 was administered orally in escalating doses on a once-daily continuous schedule in 28-day cycles to eligible patients. Samples for pharmacokinetic analyses were collected on days 1, 8, 15 and 22 of cycle 1 and day 1 of cycle 2. Anti-tumour efficacy was assessed every two cycles.
Eighty-two patients received E7080 in dose cohorts from 0.2 to 32 mg. Dose-limiting toxicities were grade 3 proteinuria (two patients) at 32 mg, and the MTD was defined as 25 mg. The most frequently observed cumulative toxicities (all grades) were hypertension (40% of patients), diarrhoea (45%), nausea (37%), stomatitis (32%) and vomiting (23%). Seven patients (9%) had a partial response and 38 patients (46%) had stable disease as best response. E7080 has dose-linear kinetics with no drug accumulation after 4 weeks' administration.
E7080 is well tolerated at doses up to 25 mg per day. Encouraging anti-tumour efficacy was observed in patients with melanoma and renal cell carcinoma.
Division of Medical Oncology, Department of Clinical Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands.
SourceBritish journal of cancer 106:10 2012 May 8 pg 1598-604
Aged, 80 and over
Maximum Tolerated Dose
Protein Kinase Inhibitors
Pub Type(s)Clinical Trial, Phase I
Research Support, Non-U.S. Gov't