Journal
BRITISH JOURNAL OF CANCER
Volume 106, Issue 10, Pages 1598-1604Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2012.154
Keywords
dose escalation; E7080; pharmacokinetics; phase I; receptor tyrosine kinase inhibitor; solid tumours
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Funding
- Eisai Inc.
- Eisai Europe Limited
- Cancer Research UK
- Chief Scientist Office, Scotland
- Cancer Research UK [11650] Funding Source: researchfish
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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. British Journal of Cancer (2012) 106, 1598-1604. doi:10.1038/bjc.2012.154 www.bjcancer.com Published online 19 April 2012 (C) 2012 Cancer Research UK
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