Adjuvant oral chemotherapy to prevent recurrence after curative resection for hepatocellular carcinoma. Postoperative adjuvant chemotherapy after curative resection of hepatocellular carcinoma: a randomized controlled trial. A randomized trial of hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma.
Adjuvant oral chemotherapy was studied in 67 patients with stage II hepatocellular carcinoma who underwent curative resection between May 1988 and December 1990. Patients were stratified into two groups according to preoperative liver dysfunction: 55 had stage I disease (mild dysfunction) and 12 had stage II (moderate dysfunction). A randomized controlled study of postoperative oral administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU) was conducted in each group. From October 1994 HCFU administration was suspended because of side-effects in nine patients with stage I liver dysfunction and in three with stage II dysfunction who had received the drug for more than 4 weeks. Cumulative survival and recurrence-free survival rates of patients with stage I disease in the treatment group were higher (P = 0.08 and P = 0.04 respectively) than those in the control group. However, in patients with stage II disease no significant difference was observed (P = 0.77 and P = 1.0 respectively). This study suggests that the potential benefits of HCFU on tumour recurrence should be weighed against the risk of adverse reactions in patients with mild liver dysfunction. To study the effect of adjuvant chemotherapy after curative hepatic resection in patients with hepatocellular carcinoma.
                A randomized controlled trial.
                A tertiary referral center.
                During a 54-month period, 142 patients with hepatocellular carcinoma underwent hepatic resection at 1 institution. Sixty-six patients who survived the operation and had no demonstrable evidence of residual disease on ultrasonographic examination and hepatic angiographic testing at 1 month after surgery agreed to participate in the study. The median follow-up time was 28.3 months.
                Thirty patients received a combination of intravenous epirubicin hydrochloride (8 doses of 40 mg/m2 each at 6-week intervals) and transarterial chemotherapy using an emulsion of iodized oil and cisplatin (3 courses with a maximum dose of 20 mL each at 2-month intervals). Thirty-six patients had no adjuvant treatment.
                Recurrence rate and disease-free survival.
                A total of 138 courses of intravenous epirubicin was given to the 30 patients. Sixty-one courses of transarterial chemotherapy were given to only 29 of the 30 patients assigned to the treatment group, because the hepatic artery in 1 patient was thrombosed. Six patients (20%) had chemotherapy-related complications with no mortality. Twenty-three of 30 patients in the treatment group and 17 of 36 patients in the control group had recurrences (P=.01). Patients who received adjuvant chemotherapy had a higher incidence of extrahepatic metastases (11 patients vs 5 patients; P=.03). The respective disease-free survival rates at 1, 2, and 3 years were 50%,36%, and 18% for the treatment group and 69%, 53%, and 48% for the control group (P=.04).
                In a group of patients who underwent curative resection of hepatocellular carcinoma, postoperative adjuvant chemotherapy using the present regimen was associated with more frequent extrahepatic recurrences and a worse outcome. A randomized trial of hepatic arterial chemoembolization was conducted in 42 patients with unresectable hepatocellular carcinoma. These patients represented 41% of patients with hepatocellular carcinoma seen during the inclusion period. In the remaining 59%, 9% had resectable tumours and 50% had unresectable tumours with contraindication for chemoembolization. Patients received either repeated chemoembolization with gelfoam powder and doxorubicin (group 1) or symptomatic treatment (group 2). There was no difference in age, prevalence of cirrhosis or staging according to Okuda between the two groups of patients. A complete tumour response (assessed by arteriography, ultrasonography and serum alphafetoprotein) was observed in four patients, and a partial response in three other patients from group 1. Actuarial survival rates were 33 and 24% in group 1 and 52 and 31% in group 2 at 6 and 12 months, respectively (differences were not significant--logrank test). With the treatment used in our study, chemoembolization did not prolong the survival time of patients with unresectable hepatocellular carcinoma. There were, however, some complete or partial responses. The high spontaneous 1-year survival rate of untreated patients was probably due to the exclusion of the most severely ill patients. Our results do not support the use of this method of chemoembolization in the treatment of hepatocellular carcinoma.
At present, there is no evidence to recommend or refute cryotherapy for patients with hepatocellular carcinoma. Randomised clinical trials with low-risk of bias may help in defining the role of cryotherapy in the treatment of hepatocellular carcinoma.