Rationale and Objectives. Dibutyryl cyclic adenosine 3',5'-monophosphate (dBcAMP) has the capacity to promote morphologic differentiation and to inhibit tumor growth in vitro, but it has not been well researched in the clinical setting. In this study we examined the effects of intraarterial infusion of dBcAMP plus mitomycin C (MMC) on long-term survival and growth inhibition of tumors. Methods. Thirty-one previously untreated patients with unresectable hepatocellular carcinoma (HCC) received intraarterial infusion of dBcAMP plus MMC. According to the International Union Against Cancer staging system, three patients had stage T3, eight had stage T4a, and 20 had stage T4b cancer. Growth inhibition was defined as no computed tomography (CT) scan evidence of increase in tumor diameter for at least 6 months after treatment. Results. In all 31 patients with HCC, the cumulative survival rate was 34% at 1 year, 14% at 3 years, and 9% at 5 years. The median survival was 5.0 months, with the longest survival period being 92 months. Among 21 patients in whom a tumor response could be evaluated on the basis of follow-up CT studies, two had complete regression of their primary tumors. Overall, the response rate was 43% (9 of 21). Among the 12 stage T4b patients who had HCC that included the main trunk and its major branches of the portal vein, portal thrombi had disappeared in four (33%). Among eight patients who survived more than 1 year and were evaluated for tumor response using follow-up CT scan studies, six (75%) had growth inhibition of tumor. Conclusion. Chemotherapy combined with dBcAMP and MMC showed a favorable response in approximately one third of 31 pateints who had unresectable HCC. Because of our results, combined therapy should be strongly considered in the treatment of patients with HCC including occlusion of the main portal vein.
