Macrocytic Anemia during Low-dose Cisplatin and 5-Fluorouracil through Implanted Infusion Port for Unresectable Hepatobilliary Malignancies

The efficacy of continuous arterial infusion chemotherapy through a subcutaneously implanted port has been reported with less adverse effects than systemic chemotherapy in hepatobilliary malignancies. However, macrocytic anemia is sometimes seen during this therapy. In 25 patients (22 with hepatocellular carcinoma, 3 with cholangiocellular carcinoma) treated with cisplatinum (10mg/day) and 5-Fluorouracil (5-FU) (250 mg/day), the frequency of anemia and its etiologies were evaluated. Moreover, the two groups ("anemia" and "no anemia" group) were compared with their backgrounds. Nine cases (36%) showed macrocytic anemia without any evident etiologies during therapy. The cumulative appearance rate of anemia was 19% at 12 weeks and 51% at 18 weeks. The Child-Pugh score or Japanese integrated staging (JIS) score were significantly higher in the "anemia" group than that in the "no anemia" group. Conclusion: Attention should be paid to slow progressive macrocytic anemia during low-dose cisplatinum and 5-FU, especially in patients with advanced liver cirrhosis. The prognosis of advanced hepatobilliary malignancies is extremely poor. Recently, the efficacy of continuous arterial infusion chemotherapy using a low-dose cisplatinum (CDDP) and 5-Fluorouracil (5-FU) via a subcutaneously implanted port has been reported in unresectable hepatocellular carcinoma (HCC) (1-4) or cholangiocellular carcinoma (CCC) (5) with improvement of the prognosis (2). Few major complications are reported with this regimen, except for nausea, leukocytopenia and thrombocytopenia, which were controllable by medical treatment without cessation of this therapy (3). However, slow progressive severe macrocytic anemia was sometimes experienced during therapy, even in patients without any other side-effects. There are no reports about the etiologies or frequency of anemia during this therapy. On the other hand, in patients with systemic full-dose 5-FU therapy, the blockade of DNA biosynthesis by 5-FU itself contributes to macrocytic anemia (6). Macrocytic anemia could occur even in our regimen through the same mechanism. Therefore, we evaluated the frequency and background of anemia in patients receiving continuous arterial infusion chemotherapies for HCC or CCC, using a low-dose CDDP and 5-FU through a subcutaneously implanted port.