Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986.

PURPOSE: To demonstrate that adding irinotecan to a standard weekly schedule of high-dose, infusional fluorouracil (FU) and leucovorin (folinic acid [FA]) can prolong progression-free survival (PFS). PATIENTS AND METHODS: Four hundred thirty patients with measurable or assessable metastatic colorectal cancer were randomly assigned to receive either FA 500 mg/m(2) as a 2-hour infusion and FU 2.6 g/m(2) by intravenous 24-hour infusion, both administered weekly for 6 weeks, followed by a 2-week rest (Arbeitsgemeinschaft für Internistische Onkologie [AIO] arm, n = 216), or a similar schedule but with FU 2.3 or 2.0 g/m(2) preceded by irinotecan 80 mg/m(2) administered over 30 minutes (experimental group, n = 214). RESULTS: The median PFS time in the experimental group was 8.5 months (95% CI, 7.6 to 9.9 months) compared with 6.4 months (95% CI, 5.3 to 7.2 months) in the AIO arm (P < .0001). The median overall survival time was increased from 16.9 to 20.1 months (P = .2779). The objective response rate was 62.2% (95% CI, 55.0% to 69.5%) in the experimental group and 34.4% (95% CI, 27.5% to 41.3%) in the AIO arm (P < .0001). CONCLUSION: The addition of irinotecan to the standard AIO FU/FA regimen was associated with a highly significant improvement in PFS and response rate and was well tolerated. The results of this study confirm that irinotecan in combination with high-dose infusional FU/FA is a reference first-line treatment.

[Incidence and spectrum of malignant disease among dialysis patients in North Bavaria]. / Inzidenz und Spektrum maligner Erkrankungen bei Dialysepatienten in Nordbayern.

BACKGROUND AND OBJECTIVE: In end-stage renal failure the incidence of cancer is increased. With regard to frequency and pattern of distribution of the tumors, there are substantial regional differences. Since this topic has to date received only minimal attention in Germany, we undertook a multi-centric analysis (8 dialysis centres) in North Bavaria in order to address the occurrence of malignant diseases in end-stage renal failure. PATIENTS AND METHODS: Of a total of 2228 patients, who underwent hemodialysis in the period from 1990 - 99 as a consequence of end-stage renal failure, the medical records of 1727 persons were analysed. Only those patients were considered, whose malignancy was diagnosed in the course of the dialysis. The Saarland cancer register served as a comparative age- and sex-matched population, with which we calculated the expected frequency of the various cancers as well as the standard incidence ratio (SIR) for the dialysis patients. RESULTS: In total 125 malignant diseases were documented. The cancer incidence was highest in the first year of treatment and was clearly lower in the subsequent periods. Of great importance was the age of the patients. The highest SIR scores were found for patients of middle age (35 - 50 years). An enhanced risk for cancer of the kidney, bladder, prostate, liver, oral cavity and the pharynx and larynx, as well as of the lymphatic and hemopoetic systems was found, while there was no or only a slight increase in the frequency of carcinoma of the mammary gland, stomach, colon-sigma-rectum and bronchial systems. CONCLUSION: The high incidence of cancer in end-stage renal failure should be given greater attention. Particularly in the high-risk group of younger dialysis patients, a regular screening - especially for tumors of the kidney, bladder and liver - appears justified.

[Induction of apoptosis by preoperative passive immunotherapy in resectable stomach carcinoma]. / Apoptoseinduktion durch präoperative passive Immuntherapie beim resektablen Magenkarzinom.

The antibody SC-1 is a human IGM molecule, which binds to a tumor specific receptor. This SC-1 receptor is detectable on biopsies, it is present in about 50% of gastric cancers. After binding of the antibody to the receptor the tumor cells go into apoptosis. 50 patients expressing the SC-1 receptor on their tumors have been treated with SC-1 prior to gastrectomy. In 80% of cases apoptosis induction could be demonstrated in the tumors. The only side effect of the SC-1 therapy was a reversible episode of fever during antibody infusion in 8% of our patients.

[New therapeutic options in chemotherapy of advanced colorectal cancer]. / Neue Therapieoptionen in der Chemotherapie des fortgeschrittenen kolorektalen Karzinoms.

BACKGROUND: Chemotherapeutic options in the treatment of advanced colorectal cancer have markedly improved during the last years. This is partly due to the high-dose 5-FU regimen, but also to the development of new cytotoxic agents and drug combinations. RESULTS: High-dose 5-FU, irinotecan, and oxaliplatin seem to be superior to low-dose 5-FU in terms of response rate and disease control. Combination of irinotecan with 5-FU/FA showed significant longer overall survival rates compared to 5-FU/FA alone in both published phase III trials. Today most patients are treated by a sequential therapeutic concept using the newer drugs mainly for second or third line therapy. However, there are reasons for the use of more intensive chemotherapy combinations in first line treatment. Combination of oxaliplatin with 5-FU/FA, that failed improvement of overall survival compared to 5-FU/FA alone, could downstage previously unresectable liver metastases for potentially curative surgery in some patients. Oral fluoropyrimidines mark another progress in the treatment of advanced colorectal cancer. They seem to be comparable to low-dose 5-FU/FA and could ease chemotherapy. PERSPECTIVE: Prospective randomized phase III trials must confirm the best chemotherapy and the best strategy for the different subgroup of patients.

Adjuvant therapy for gastric adenocarcinoma with the apoptosis-inducing human monoclonal antibody SC-1: first clinical and histopathological results.

In a first clinical trial with the apoptosis-inducing human antibody SC-1 eight patients with poorly differentiated stomach adenocarcinoma of diffuse-type received 20 or 30 mg of purified SC-1 antibody intravenously, followed 24 or 48 h later by gastrectomy and lymphadenectomy. In seven cases a significant induction of apoptotic activity was measured in primary tumors as compared with earlier biopsy material and in five patients a significant regression of tumor mass could be determined histopathologically. No toxic crossreactivity was observed with normal tissue or organs of patients.

Lysis of human immunodeficiency virus type 1 antigen-expressing cells by CD4 and CD8 T cells ex vivo.

The aim of this study was to investigate the extent of lysis mediated by cytotoxic T lymphocytes (CTL) directed against human immunodeficiency virus (HIV) type 1 gag protein and envelope glycoprotein in peripheral blood mononuclear cells (PBMC) from HIV-1-infected subjects and to compare it with nonspecific envelope glycoprotein-directed cytotoxicity involving CD4 T cells. Most seropositive subjects exhibited antigen-specific cytotoxicity directed at one or both viral antigens in unstimulated or in vitro-stimulated PBMC (or both) mediated by CD8 T cells. In addition, all donors, including seronegative control persons, exhibited nonspecific calcium-independent cytotoxicity involving CD4 T cells and envelope glycoprotein-expressing cells. No calcium-dependent, antigen-specific CD4 T cell-mediated cytolysis was detected. In seropositive subjects, the vigor of nonspecific cytotoxicity was comparable to lysis by antigen-specific CD8 CTL and suggests that it may contribute to lysis of HIV-infected cells in vitro and in vivo.