Phase II study of mitonafide in non-small cell lung cancer (NSCLC)

Summary

Background: The new intercalative agent Mitonafide was shown in early clinical trials to be toxic to the central nervous system when administered as a short intravenous infusion, but not when given as a 120-hour continuous infusion. Thus, clinical development in different tumor types was pursued using only this administration schedule,

Patients and methods: Forty-nine patients with previously untreated non-small cell lung cancer(NSGLC) and at least one measurable site received Mitonafide as a 120-hour continuous (5 days) infusion every 3 weeks. The starting dose was 170 mg/m²/day × 5 in the first 26 patients and 200 mg/m²/day × 5 in the remainder. Patients were evaluated for toxicity after each course and for response every two courses and remained on treatment until excessive toxicity or disease progression were observed. A special test, the “Mini-mental state”, was used to assess patients' cognitive functions.

Results: Of the 49 patients entered, 42 were evaluable for response and toxicity. Toxicity consisted mainly of myelosuppression and no neurologic side effects were observed. Only one patient presented a partial response.

Conclusions: Although definitively safe with this schedule of administration, Mitonafide is not active in NSCLC.