A prospective randomized study comparing high- and low-dose leucovorin combined with same-dose 5-fluorouracil in advanced colorectal cancer.

Although the efficacy of 5-fluorouracil (5-FU) modulated by leucovorin is well established for advanced colorectal cancer, the question of the most effective regimen and optimal dose of leucovorin remains unanswered. This prospective randomized trial compares low-dose (group 1) and high-dose (group 2) leucovorin, combined with the same dose of 5-FU to determine whether high-dose leucovorin was more beneficial than low-dose on overall survival. Inclusion criteria were: unresectable metastatic colorectal carcinoma, with or without evaluable tumor response; a performance status of less than grade 3 (World Health Organization classification); and no previous chemotherapy for metastases. Forty-two patients were randomized in group 1 (leucovorin, 20 mg/m2/day, days 1 through 5) and 41 patients in group 2 (leucovorin, 200 mg/m2/day, days 1-5). All the patients in the two groups received a 1-hour infusion of 400 mg/m2/day 5-FU every 4 weeks. The two groups were matched with no statistically significant differences in gender ratio, site of primary tumor, performance status, and tumor extent. Toxicity in the two regimens was low and not significantly different between the two groups. Overall median survival was 346 days in group 1 and 323 days in group 2 and was not significantly different between the two groups. At 1 year, the test of equivalence was significant (p < 0.01), demonstrating an absence of more than 20% benefit in 1-year survival for the high-dose regimen. The use of high-dose leucovorin combined with 5-FU in the 5-day regimen does not significantly improve overall survival for patients who have metastatic colorectal cancer.

[Autoimmune hepatitis]. / Les hépatites auto-immunes.

Acute and chronic autoimmune hepatitis are uncommon inflammatory liver diseases, mainly occurring in young women, in association with hypergammaglobulinemia and serum autoantibodies. Different types have been described: type 1 characterized by anti-smooth muscle and anti-nuclear antibodies; type 2 characterized by anti-LKM1 antibodies; type 3 characterized by anti-SLA antibodies. Other types, still not clearly defined, may exist. Autoimmune hepatitis are associated with HLA A1 B8 DR3 and HLA DR4. Without any treatment, the disease leads to cirrhosis and, uncommonly, to fulminant hepatitis. Large doses of corticosteroids usually allow to control the disease. Relapse of hepatitis is frequent after corticosteroid withdrawal. Concomitant administration of immunosuppressive agents such as azathioprine allows to reduce corticosteroid dosage and contributes to maintain the remission of the disease. Liver transplantation may be indicated in cases of severe cirrhosis or fulminant hepatitis.

[Autoimmune biological anomalies in 35 patients with chronic viral hepatitis C treated over 6 months with interferon and followed-up over a year]. / Anomalies biologiques autoimmunes chez 35 malades atteints d'hépatite chronique viral C traités pendant six mois par interféron (IFN) et suivis pendant un an.

Several clinical or biological autoimmune disorders, particularly lupoid diseases, are associated with chronic hepatitis C. They may be exacerbated by alpha IFN, but they are not involved in the response to therapy.

[Chronic viral hepatitis C and interferon: results after a year and predictive factors of response (a multivariate study with 35 patients)]. / Hépatite chronique virale C et interféron: résultats à un an et facteurs prédictifs de réponse (étude multivariée sur 35 sujets).

Six months alpha IFN therapy was efficient for chronic viral hepatitis C in 31% patients after six months and in 17% after one year. Cirrhosis, low serum albumin or prealbumin levels and elevated IgA seric level were non responsiveness predictive factors.