A RANDOMIZED PHASE-II TRIAL OF AMONAFIDE OR TRIMETREXATE IN PATIENTS WITH ADVANCED NONSMALL CELL LUNG-CANCER - A TRIAL OF THE NORTH-CENTRAL-CANCER-TREATMENT-GROUP

Background. In an effort to identify new active chemotherapeutic agent s against non-small cell lung cancer (NSCLC), the authors conducted a randomized Phase II trial to evaluate the efficacy of amonafide or tri metrexate in patients with Stage IV disease. Methods. This was a multi center Cooperative Oncology Group trial. All patients had advanced NSC LC and were previously untreated with chemotherapy. Patients were rand omized to treatment after enrollment. Amonafide was administered as a 24-hour continuous infusion (1600 mg/m2) every 21 days. Trimetrexate ( 150 mg/m2) was administered intravenously over 30 minutes every 2 week s. The primary endpoints of the study were clinical response and toxic effects. All patients were observed for survival. Results. Thirty-fiv e patients received amonafide and were assessable. There were no compl ete responses and two partial responses (6%). Thirty-seven patients we re treated with trimetrexate. There were no complete responses and fiv e (14%) partial responses. Myelosuppression was the primary toxic effe ct observed with amonafide treatment. Trimetrexate was associated infr equently with clinically significant side effects. Conclusions. Amonaf ide is inactive against NSCLC, and no additional studies with this age nt are planned. Trimetrexate has some activity against NSCLC, but its role in the future therapy of this disease is questionable.