Tumor necrosis factor alpha sensitizes low epidermal growth factor receptor (EGFR)-expressing carcinomas for anti-EGFR therapy.

Analysis of 1,060 xenotransplants derived from cancer cell lines as wel as spontaneously occurring tumors from the larynx, pharynx, mammary gland, uterine cervix, and vulva revealed that tumor regression induced by treatment with monoclonal antibodies (EMD 55900 and EMD 72000 against the epidermal growth factor receptor (EGFR) could be enhanced by tumor necrosis factor alpha (TNF-alpha) treatment in vivo. Moreover, tumor that primarily do not respond to antibody treatment can be made suscep tible by additional TNF-alpha treatment. To investigate the in vivo effects of monoclonal antibodies, we treated tumors derived from cell lines (A431 and Detroit 562) as well as spontaneously occurring squamous cell carci nomas and adenocarcinomas (transplanted on NMRI-nu/nu mice) gener ally with EMD 55900 (40 microg/g mouse) and its humanized version EMD 72000 (40 microg/g mouse). When treated with EMD 55900 and EMD 72000 carcinomas with an EGFR concentration of > or = 70 fmol/mg protein showed significant reduction in tumor size compared with untreated controls. The degree of tumor regression correlated with the EGFR concentration of the tumor. In mice treated with TNF-alpha (0.5 microg/g mouse) and EMD 55900 72000 simultaneously, we observed enhanced antitumor effects up to complete tumor eradication. Carcinomas with an EGFR concentration <70 fmol/mg protein could be made susceptible to treatment with EMD 55900 and EMD 72000 by simultaneous treatment with TNF-alpha, resulting in a significant reduction in tumor size.

Predictors for long-term survival after interdisciplinary salvage surgery for advanced or recurrent gynecologic cancers.

BACKGROUND AND OBJECTIVES: We wanted to identify factors which allow predicting long-term survival after pelvic exenteration (PE) for locally advanced or recurrent gynecologic malignancies. METHODS: All patients undergoing PE at our institution from 1983 to 2002 were screened. In 203 cases data were obtainable and analyzed with respect to factors predicting outcome considering morbidity, mortality, and survival. Follow-up data and data concerning late complications not documented in our records were obtained by telephone interviews. RESULTS: Mean age was 55 (22-77) years. PE was performed for locally advanced (36%) or recurrent (64%) cervical (n = 133), endometrial (n = 26), vaginal (n = 23), vulvar (n = 10), and ovarian cancer (n = 11, cases with rectum and/or bladder resections). In 13.4% (n = 26) the intent of the procedure was palliation in the remaining cure. Procedures performed were anterior (n = 91), posterior (45), or total (n = 67) PE. 53% of patients underwent preoperative radio-chemotherapy, 11.8% as a neoadjuvant treatment. Mean OR time was 8.1 hr, an average of 5.6 units of packed red blood cells were perioperatively transfused. Microscopically complete resection was achievable in n = 69 patients. Perioperative mortality was 1% (n = 2). Seventy-one percent (n = 144) of patients were available for follow-up. Five-year overall survival in patients treated with a curative intent was 21%, 5-year survival in those patients with complete resection was 32%. Forty-two percent of patients with a complete resection without lymph node involvement, age 30-50, curative intention, and the absence of a pelvic sidewall infiltration survived 5 years or longer. CONCLUSION: In our series a 5-year survival rate of over 40% could be achieved for nodal-negative patients without pelvic sidewall infiltration when treated with curative intent and after complete resection.