A phase I study of E7080, a multitargeted tyrosine kinase inhibitor, in patients with advanced solid tumours
| Autor: | William Copalu, A. Mazur, Jantien Wanders, M Keesen, R. Morrison, D. S. Boss, Jos H. Beijnen, J P O'Brien, Jan H.M. Schellens, Hilary Glen, Thomas J. Evans, B Tait |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Maximum Tolerated Dose medicine.drug_class Biology Tyrosine-kinase inhibitor Internal medicine Neoplasms Protein-Tyrosine Kinases medicine Humans In patient Protein Kinase Inhibitors solid tumours Aged Aged 80 and over Phenylurea Compounds receptor tyrosine kinase inhibitor phase I Middle Aged Phase i study Clinical trial Endocrinology Oncology Maximum tolerated dose dose escalation Cancer research Clinical Study Quinolines E7080 Female pharmacokinetics |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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