IngentaConnect Phase I and pharmacokinetic study of E7070, a novel sulfonamide, ...

Authors: Punt C.J.A.¹; Fumoleau P.²; Walle B.v.d.¹; Faber M.N.³; Ravic M.⁴; Campone M.²

Source: Annals of Oncology, Volume 12, Number 9, September 2001 , pp. 1289-1293(5)

Publisher: Springer

Abstract:

Background: E7070 is a novel antitumor sulfonamide which blocks the cell in G1 phase. A phase I study was initiated to investigate the toxicity, maximum tolerated dose (MTD), and pharmacokinetics of this compound when administered intravenously at a daily times five schedule once every three weeks.

Patients and methods: Patients with solid tumors not amenable to standard forms of therapy were eligible. E7070 was administered to cohorts of 3–6 patients per dose level, the starting dose was 10 mg/m^2/day. Dose escalation was performed according to a Fibonacci-like scheme.

Results: Thirty-three patients entered the study. At E7070 doses of 200 and 160 mg/m^2/day dose-limiting toxicities occurred, which consisted of febrile neutropenia, thrombocytopenia, diarrhea, skin folliculitis, asthenia, and stomatitis. The pharmacokinetic profile of E7070 at this schedule is non-linear with increasing dose. A partial response was observed in a patient with heavily pretreated breast cancer. Disease stabilizations and some minor responses were also documented.

Conclusions: Myelosuppression is the predominant toxicity of E7070. Clinical efficacy with E7070 was observed. The recommended dose for further studies at this daily times five schedule is 130 mg/m^2/day.

Keywords: E7070; cancer; chemotherapy; pharmacokinetics; phase I; sulphonamide

Language: English

Document Type: Regular paper

Affiliations: 1: Department of Medical Oncology, University Medical Center St. Radboud, Nijmegen, The Netherlands 2: Department of Medical Oncology, Centre René Gauducheau, Nantes, France 3: NDDO Oncology, Amsterdam, The Netherlands 4: Eisai Limited, London, UK

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Phase I and pharmacokinetic study of E7070, a novel sulfonamide, given at a daily times five schedule in patients with solid tumors. A study by the EORTC-Early Clinical Studies Group (ECSG)