Phase I trial with weekly EO9, a novel bioreductive alkylating indoloquinone, by the EORTC Early Clinical Study Group (ECSG)

Purpose: EO9 is a new synthetic bioreductive alkylating indoloquinone, with preferential activity against solid tumors and higher antitumor activity u nder anaereobic conditions compared with aerobic conditions. In preclinical models EO9 demonstrated no major organ toxicity. The aim of the present ph ase I study was to determine the toxicities and the maximal tolerated dose (MTD) of EO9 administered as a 5-min i.v. infusion weekly to patients with solid cancers. Methods: Twenty-eight patients entered the study. The dose w as escalated from 2.7 mg/m(2) according to a Fibonacci-like schedule. Resul ts and conclusion: The dose-limiting toxicity was proteinuria. No other maj or toxicities were detected and in particular there was no significant incr ease in serum creatinine. This was in contrast to findings in a previous ph ase I trial using EO9 in a 3-weekly schedule, where a number of patients ex perienced severely decreased kidney function. The MTD in the present study was 15.0 mg/m(2) weekly and the recommended dose for phase II studies was 1 2.0 mg/m(2) weekly. Compared with 3-weekly EO9, the dose intensity could be increased from 22 mg/m(2) to 36 mg/m(2) with the weekly administration. Ph ase II studies have been performed by the EORTC Early Clinical Study Group in advanced breast, gastric, colorectal, pancreatic, and non-small-cell lun g cancer.