EFFECT OF RA-233 (MOPIDAMOLE) ON SURVIVAL IN CARCINOMA OF THE LUNG AND COLON. FINAL REPORT OF VA COOPERATIVE STUDY #188

RA-233 (mopidamole) is a phosphodiesterase inhibitor that has been shown previously to limit progression of malignancy in certain experimental animal models and in a pilot study in humans. RA-233 plus chemotherapy was compared with chemotherapy alone in a five-year double-blind trial involving 719 patients with advanced carcinoma of the lung and of the colon. No difference existed between treatment groups for a variety of demographic, clinical, and laboratory parameters evaluated at entry to the study. There were no instances of unblinding and no patients were lost to followup. Minimum followup was 1 year. Patients ingested RA-233 or placebo for over 85% of their total survival interval and took 66% of the number of pills originally prescribed. RA-233 treatment was associated with a statistically significant prolongation of survival in patients with non-small cell lung cancer limited to one hemithorax, and also with reduction in mean plasma fibrinogen concentration, and with reduction in the incidence of bleeding episodes. RA-233 was not toxic.The favorable effects on survival could not be explained by any factor other than the RA-233 treatment. In other tumor categories tested no differences in survival were observed. These results suggest that RA-233 may be useful in the treatment of non-small cell lung cancer of limited extent (and possibly other tumor types). They also suggest that therapeutic intervention aimed at modified pathways within tumor cells might constitute an innovative investigational approach to the treatment of cancer.