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Br J Cancer. 2012 May 8;106(10):1598-604. doi: 10.1038/bjc.2012.154. Epub 2012 Apr 19.

A phase I study of E7080, a multitargeted tyrosine kinase inhibitor, in patients with advanced solid tumours.

Author information

1
Division of Medical Oncology, Department of Clinical Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

PMID:
22516948
PMCID:
PMC3349182
DOI:
10.1038/bjc.2012.154
[Indexed for MEDLINE]
Free PMC Article

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