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

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.

Forty-nine patients with previously untreated non-small cell lung cancer (NSCLC) 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 x 5 in the first 26 patients and 200 mg/m2/day x 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.

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.

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