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).

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/m2/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/m2/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/m2/day.