Intrahepatic arterial infusion of combination of mitomycin-C and 5-fluorouracil in treatment of primary and metastatic liver carcinoma

Abstract

improvement in drug response and reduction of toxicity were observed after continuous intrahepatic arterial infusion of mytomycin-C (MMC) and 5-fluorouracil (5-FU) in 15 of 26 patients with primary or metastatic carcinoma of the liver. Serum bilirubin values of 10 mg/100 ml absence of ascites, extreme cachexia and impending hepatic failure were used as the criteria for admission of these patients into the study. The patients were given MMC in a dose of 0.08 mg/kgon day 1,5-FUin a dose of8-10 mg/kgon days2-5,and MMCon day6. This schedule was reinitiated on days 8 and 15 for a total mean duration of 18 days. Maintenance therapy was carried out by the administration of these drugs at induction dosage alternated each week as a single 24 hourly intravenous infusion. Objective response to combination therapy was defined as decrease of at least 50% in the liver size and in the abnormal levels of serum alkaline phosphatase and glutamic oxaloacetic transaminase (SGOT) , and near normal levels of serum bilirubin for a minimum period of 2 months. The duration of objective response ranged from 3-16 months with a median of8.2 months. The median survival time for the responders was 7.2 months for patients with primary carcinoma and 9.4 months for patients with metastatic carcinoma of the liver as compared to 2 months for patients who failed to respond to the treatment. Five out of 12 patients who were refractory to MMC or 5-FU by intravenous infusion responded to the present combination drug therapy. Of four patients who died during induction therapy, three had liver failure and the fourth suffered pulmonary embolism. These studies provide evidence that combination therapy with MMC and 5-FU increases the survival time of patients with hepatic cancer, presumably due to the synergistic action of these drugs which permits the use of a low dosage schedule and has less toxic effects.Cancer 39:1425-1429, 1977. shown to be effective individually in primary and metastatic hepatic tumors. Earlier studies have indicated synergistic effects of the combination of MMC and 5-FU by inhibition of the murine Sa-180 and ascitic leukemia, L-1210. l9 I n our investigations the use of combination therapy with MMC and 5-FU by intra-arterial infusion was found effective in the treatment of patients with advanced oral carcinoma. These observations prompted a prospective study to evaluate the chemotherapeutic effectiveness of intrahepatic arterial infusion of MMC and 5-FU in patients with primary and metastatic carcinoma of the liver. NTRAHEPATIC ARTERIAL INFUSION T H E R

Gallbladder cancer

“…Hepatic arterial infusion of 5-FU plus mitomycin has also been used. We treated 26 patients with hepatic metastases from GBC by intraarterial infusion of 5-FU plus mitomycin; the overall response rate was 34% [37,38]. Most nonresponders had diffuse hepatic metastases.…”

Systemic And Regional Chemotherapy For Advanced Hepatobiliary Carcinomas

“…The responders survived significantly longer than nonresponders (median 6 versus 1 month). Misra et al treated 13 patients with advanced gallbladder cancer using intrahepatic arterial infusion with 5-FU and mitomycin C. 38 Nine of 13 patients had an objective response defined as at least 50 percent decrease in the liver size and in the abnormal levels of serum alkaline phosphatase and glutamic oxaloacetic transaminase and near normal levels of serum bilirubin for a minimum period of 2 months. Their survival periods ranged from 4.6 to 14 months.…”

Design, synthesis, and in vitro evaluation of cytotoxic activity of new substituted 1,4-benzoquinones and hydroquinones

“…Among the most important biological activities reported are anticancer (Radeke et al, 1997;Rozek et al, 2001;Stahl et al, 2001;Afrasiabi et al, 2005;Ward et al, 2005;Hasinoff and Begleiter, 2006), antimicrobial (Chabaan et al, 1984a(Chabaan et al, ,b, 1989Kaneshiro et al, 2000;Habib and Mahran, 2004;Tapia et al, 2004), antiviral (Urbam andCapon, 1996;Iwashima et al, 2005), and anti-inflammatory (Ospina et al, 2001) activities. Mitomycins comprise a group of substituted indoloquinone antibiotics with potent antitumor activity (Iyer and Szyblaski, 1963;Misra et al, 1977). These compounds act as bifunctional alkylating agents that add across both strands of the DNA double helix leading to cancer cell death (Iyer and Szyblaski, 1963).…”