Intraarterial infusion of dibutyryl cyclic adenosine monophosphate plus mitomycin C for unresectable hepatocellular carcinoma: long-term survival and response to tumor growth inhibition.
OBJECTIVE
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.


CONCLUSIONS
Chemotherapy combined with dBcAMP and MMC showed a favorable response in approximately one third of 31 patients 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.
Kusano
S
S
Department of Radiology, National Defense Medical College, Saitama, Japan.
Katayama
M
M
Uematsu
M
M
Kaji
T
T
Kosuda
S
S
Endo
T
T
Sugimoto
M
M
Ishii
K
K
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003994:Bucladesine / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016685:Mitomycin / Q000008:administration & dosage; D018709:Statistics, Nonparametric; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
D000903:Antibiotics, Antineoplastic; D016685:Mitomycin; D003994:Bucladesine