Hepatic arterial infusion of Corynebacterium parvum and chemotherapy

Metastatic malignant lesions confined to the liver, often refractory to intravenous chemotherapy, may respond to hepatic arterial infusion of chemotherapy. To further improve remission and survival in patients with metastatic disease of the liver, hepatic arterial infusion of combination immunotherapy and chemotherapy was initiated in a pilot study. Thirty patients with disease predominantly or completely confined to the liver received 63 hepatic arterial infusion treatment cycles. A hepatic arterial catheter was placed by the percutaneous route or at laparotomy. Sixteen patients with metastatic carcinoma of the colon were treated with Corynebacterium parvum followed by floxuridine. Eleven of these received ≥2 treatment cycles and are, thus, evaluable for response. Eight of these 11 patients, with tumor refractory to prior systemic fluorouracil, had objective regression of metastatic tumor of the liver - three partial remissions and five regressions, less than partial remission. Of 14 patients with varied primary tumors treated with hepatic arterial infusion of various chemotherapy regimens, significant antitumor responses were seen in two patients with carcinoma of the breast, partial remission and less than partial remission, and one patient with hepatoma, partial remission. Major complications related to arterial catheterization were two episodes of Staphylococcus aureus endarteritis and four incidences of hepatic arterial occlusion. Corynebacterium parvum related toxicity included hepatomegaly with tenderness, fever, chills and a minimal decrease in platelet count. Additionally, an immediate hepatic toxicity was noted in one-third of the Corynebacterium parvum treatment cycles and resolved without major complications. Delayed hepatic toxicity was also noted in three patients. Chemotherapy toxicity manifested as mucositis and myelosuppression was unacceptable when floxuridine was given with adriamycin-deoxyribonucleic acid complex. However, floxuridine - 100 milligrams per square meter per day for five days - by hepatic arterial infusion was well tolerated with minimal mucositis as the major side-effect. The hepatic arterial infusion of Corynebacterium parvum plus floxuridine appears a promising therapeutic approach in metastatic carcinoma of the colon with an encouraging response rate and acceptable toxicity. The potential benefits of Corynebacterium parvum need to be determined in future clinical trials.