Induction cisplatin-irinotecan followed by concurrent cisplatin-irinotecan and radiotherapy without surgery in oesophageal cancer: multicenter phase II FFCD trial.

A recent phase I study showed that weekly cisplatin, irinotecan and concurrent radiotherapy can be administered with moderate toxicity in patients with oesophageal cancer. Patients with no prior treatment and oesophageal cancer stage I to III, performance status <3, caloric intake >1,500 kcal day(-1) were included. Chemotherapy, with cisplatin 30 mg m(-2) and irinotecan 60 mg m(-2), was administered at days 1, 8, 22, 29, and concurrently with radiotherapy at days 43, 50, 64 and 71. Radiotherapy was delivered with 50 or 50.4 Gy in 25 fractions/5 weeks. Forty-three patients were included, 10 stage I, 19 stage II and 14 stage III. Mean age was 59.2 years (range 44-79). A total of 30 out of 43 (69.8%) patients underwent all planned treatment. During induction chemotherapy, 14 severe toxicities of grade 3 or 4 in 10 patients (23.3%) were reported with 57.1% due to haematoxicity. During chemoradiotherapy, 31 severe toxicities of grade 3 or 4 with 64.5% due to haematotoxicity were reported in 18 patients. One toxic death occurred (diarrhoea grade 4). The complete clinical response rate was 58.1% (95% CI: 43.4-72.8%). Overall survival rate at 1 and 2 years was 62.8%, (95% CI, 58.3-77.3%) and 27.9% (95% CI, 13.4-41.3%), respectively. In conclusion, cisplatin-irinotecan-radiotherapy is an active and well-tolerated regimen feasible in out-patients.

Prognostic factors in patients with hepatocellular carcinoma. Attempts for the selection of patients with prolonged survival.

A prognostic study based on 127 untreated patients with hepatocellular carcinoma was undertaken to evaluate their survival time and to find clinical and biologic criteria which allow the selection of patients with a survival time longer than 60 days who could enter a therapeutic trial. Twenty-eight clinical and biologic variables were assessed using univariate and multivariate semiparametric regression (Cox's) models. Ten variables were isolated by univariate analysis. Multivariate analysis found a negative relationship between a survival time longer than 60 days and five of these variables; these variables were in decreasing order: encephalopathy, alcohol consumption, aspartate amino transferase (AST), blood urea nitrogen, and total bilirubin. Prevalence, positive, and negative predictive values of encephalopathy were 20%, 27.5%, and 97% respectively. When three other criteria: ASAT greater than four times the upper limit of the normal (N), blood urea nitrogen greater than N, and total bilirubin greater than 2N were added, their prevalence, positive, and negative predictive values were 72%, 89.7%, and 57.1% respectively. These results suggest that in countries where incidence of hepatocellular carcinoma is low and recruitment of patients difficult, absence of encephalopathy must be the only criterion for selection of patients with hepatocellular carcinoma in therapeutic trials; whereas, in countries with a high incidence of hepatocellular carcinoma the other criteria may be added.

[Relation between serum markers of hepatitis B virus and alpha fetoprotein in hepatocellular carcinoma in France]. / Relations entre marqueurs sériques du virus de l'hépatite B et alphafoetoprotéine dans les carcinomes hépatocellulaires en France.

Prevalences of serum markers of hepatitis B virus and alphafetoprotein levels were investigated in 96 patients with hepatocellular carcinoma. Serum HBs Ag was present in 17 patients (17.5 p. 100), anti-HBc antibody alone in 10 patients (10.5 p. 100), and anti-HBs antibody with or without associated anti-HBc antibody in 32 patients (33.5 p. 100). Serum alphafetoprotein levels were increased (greater than 20 ng/ml) in 71 patients (74 p. 100). Serum alphafetoprotein levels were significantly higher in patients with than in patients without serum HBs Ag. Serum alphafetoprotein levels above 1,000 ng/ml were more frequently found in patients with serum HBs Ag or anti-HBc antibody than in other patients. These results suggest the presence of a link between HBs Ag and alphafetoprotein in hepatocellular carcinoma.

[Hepatocellular carcinoma in France. Clinical, biological and virological aspects in 197 patients]. / Carcinomes hépato-cellulaires en France. Aspects cliniques, biologiques et virologiques chez 197 malades.

The authors report the clinical and biological features in 197 patients with hepatocellular carcinoma seen in two French hospitals. Mean age was 63 +/- 12 years. Eighty-nine per cent were men. Cirrhosis was present in 88 p. 100. Alcoholic liver disease was associated with hepatocellular carcinoma in 71.5 p. 100. At the time of diagnosis, ascites was present in 62 p. 100 of the patients, jaundice in 49 p. 100, encephalopathy in 20 p. 100 and gastrointestinal bleeding in 12.5 p. 100. Twenty patients (10 p. 100) did not have any of these complications. An increase in serum gammaglutamyl transpeptidase and ASAT was the most frequent biological abnormality observed in 96 and 94 p. 100 of patients respectively. Hypercalcemia and a high hematocrit were present in 5 and 6 p. 100 of patients respectively. Serum HBs Ag (RIA) was present in 17.5 p. 100 of patients, anti-HBc in 50 p. 100 and anti-HBs in 33.5 p. 100; 38.5 p. 100 of patients had no serum HBV marker. Serum alphafetoprotein levels were higher than 20 ng/ml, 250 ng/ml and 1,000 ng/ml in 76.5 p. 100, 43.5 p. 100 and 33 p. 100 of patients respectively. There were no relationships between the presence of serum markers of HBV or high alphafetoprotein levels and clinical and biological data. These results confirm that the clinical, biological and virological aspects of hepatocellular carcinoma in France are similar to those reported in other western countries.

Intrinsic hepatic clearance and Child-Turcotte classification for assessment of liver function in cirrhosis.

Child-Turcotte classification (CTC) is an empirical but widely accepted approach for assessment of severity of cirrhosis. However, it is not known to what extent CTC reflects accurately the degree of impairment of hepatic function. In this study we compared CTC, standard liver tests and intrinsic hepatic clearance (IHC) of indocyanine green as means of assessing hepatic function in 63 cirrhotic patients. As compared to 10 control patients, IHC was significantly decreased in the cirrhotic group: (mean +/- SD) 0.270 +/- 0.141 l/min vs 1.227 +/- 0.312 l/min (P less than 0.001). Serum bilirubin (SB), prothrombin time (PT) and serum albumin were significantly correlated with the degree of IHC impairment while alkaline phosphatase, ALAT and clinical criteria of CTC were not. Multivariate analysis showed that SB and PT were the only 2 variables that significantly explained the impairment of IHC. The model which best explained IHC impairment was Z = 21.77 + 4.78 PT - 1.25 SB. The rate of IHC variance explained by this model, as determined by multiple correlation coefficient square (R2), was 42.6%. These results suggest that CTC provides only gross information about the degree of impairment of liver function in cirrhosis. To evaluate the role of liver function in the prognosis or in the response to treatments, it should therefore be preferable to employ direct measurement of liver function using a clearance technique.