PHASE-II STUDY OF MITONAFIDE IN ADVANCED AND RELAPSED COLORECTAL-CANCER

Background. This study investigated the antitumoral activity in colore ctal cancer and toxicity of a 5-day continuous infusion of a new cytos tatic agent, Mitonafide, that had previously shown to be neurotoxic wh en administered as a short daily x 5 days infusion. Patients and metho ds. Seventeen chemotherapy-naive patients with advanced or relapsed co lorectal cancer and measurable disease entered the study. All but one received a 120-hour (5-day) continuous infusion of Mitonafide at a sta rting dose of 200 mg/m(2)/day every 3 weeks. Toxicity evaluation was p erformed after each course and response assessment every 2 courses usi ng the standard World Health Organization (WHO) criteria completed by the ''Mini-mental state'' test for cognitive status examination. Resul ts. Sixteen patients received a total of 41 courses of Mitonafide whic h resulted to be severely myelotoxic. In total, 13/16 patients had WHO grade 3-4 neutropenia, 7 of them with infection, and the treatment ha d to be stopped in 3 patients after only 1 course due to excessive tox icity. No central nervous system toxicity was observed. No objective r esponses were evidenced. Conclusions. At the dose and schedule of admi nistration used, Mitonafide is not active in colorectal cancer and ind uces severe myelotoxicity thus not deserving further studies in this i ndication.