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Biomedical subjects

E Holz

Publications and source records attributed to E Holz.

16 recordsLinked to original sources
PubMed1998

Diagnosis and therapeutic relevance of micrometastases.

The disseminated isolated tumor cell has become a formidable object of solid tumor research for at least three good reasons: it can be identified in organ compartments such as bone marrow, blood, and lymph nodes and, once found, it can be morphologically characterized with respect to tumor-associated antigens, oncogenes, tumor suppressor genes, proliferation markers, and/or growth receptors. Thirdly, it is also an ideal target for immunotherapy directed at accessible, well-defined membrane-associated antigens of the tumor cell.

Antigens, Neoplasm↗
PubMed1998

Monoclonal antibody therapy for resected Dukes' C colorectal cancer: seven-year outcome of a multicenter randomized trial.

PURPOSE: As previously shown, antibody treatment increased survival of patients with resected colorectal cancer of stage Dukes' C. Since the 5-year analysis was criticized because of the wide range (2.7 to 7.5 years) of follow-up time, we performed a 7-year analysis with only four of 189 patients monitored for less than 5 years. PATIENTS AND METHODS: A total of 189 patients with resected Dukes' C colorectal cancer were randomly allocated to infusions of a total of 900 mg 17-1A antibody, 500 mg postoperatively followed by 4 monthly doses of 100 mg (n=99), or to observation only (n=90). Primary end points were overall survival and disease-free interval. Patients were stratified by a dynamic randomization according to center, sex, location of tumor, number of affected lymph nodes, and preoperative carcinoembryonic antigen concentration. RESULTS: Randomization produced balanced distribution of risk factors. After 7 years of follow-up evaluation, treatment had reduced overall mortality by 32% (Cox's proportional hazard, P < .01; log-rank, P=.01) and decreased the recurrence rate by 23% (Cox's proportional hazard, P < .04; log-rank, P=.07). The intention-to-treat analysis gave a significant effect for overall survival (Cox's proportional hazard, P < .01; log-rank, P=.02) and disease-free survival (Cox's proportional hazard, P=.02; log-rank, P=.11 ). While distant metastases were significantly reduced (Cox's proportional hazard, P=.004; log-rank, P=.004), local relapses were not (Cox's proportional hazard, P=.65; log-rank, P=.52). This differential effect of 17-1A antibody on disseminated isolated tumor cells versus occult local satellites may explain the increased significance seen in the overall survival. CONCLUSION: The now-matured study shows that 17-1A antibody administered after surgery prevents the development of distant metastasis in approximately one third of patients. The therapeutic effect is maintained after 7 years of follow-up evaluation.

Adenocarcinoma↗
PubMed1996

Antibody-based immunotherapeutic strategies in colorectal cancer.

Monoclonal antibodies may well be on their way to becoming an integral part of therapy after the most recent success in prolonging overall and recurrence-free survival in patients with stage III colorectal cancer after potentially curative surgery. After a median follow-up of 5 years, antibody treatment reduced the overall death rate by 30% and decreased the recurrence rate by 27%. These results are similar with regard to efficacy but there is less toxicity with those obtained in contemporary and more recent chemotherapy trials. The key to success with high-molecular-weight substances such as immunoglobulines lies in the careful selection of the appropriate target population, i.e., patients with minimal residual disease, where only isolated tumor cells which are readily accessible to therapy are present. An argument for combining immunotherapy with chemotherapy can be made on the basis of the phenotype of individual disseminated tumor cells, which by immunocytochemistry were found to only rarely express proliferation-associated antigens and therefore are independent of the cell cycle. Further efforts to improve immunotherapy have also led to the combined clinical use of antibodies with biologic response modifiers which are known to enhance effector cell-mediated antibody-dependent cytotoxicity. Additional rationally designed clinical trials are ongoing in which specific immunotherapy is directed towards known, readily accessible, and abundant cell target structures, either alone or combined with treatment modalities which employ different action mechanisms.

Animals↗