ABSTRACT
BACKGROUND: Nasal polyposis frequently occurs within the clinical picture of aspirin-exacerbated respiratory disease (AERD). A derailed arachidonic acid metabolism is regarded to be part of the pathophysiology of AERD, and aspirin desensitization is the only causal therapeutic option, so far. The optimal maintenance dose of aspirin desensitization to prevent nasal polyp recurrence on the one hand and to minimize aspirin-related side-effects, on the other hand, is still a matter of debate. The aim of this trial was to investigate the efficacy and safety of a low-dose aspirin desensitization protocol. METHODS: After sinus surgery, 70 individuals with AERD were randomly allocated to a prospective double-blind placebo-controlled aspirin desensitization protocol with a maintenance dose of 100 mg daily. The primary outcome was polyp relapse after 36 months. Nasal endoscopy status, quality of life, and patients' symptom score as well as aspirin-related side-effects were monitored. RESULTS: Due to the high dropout rate, only 31 individuals were evaluated. After 36 months, nasal polyp relapse was less frequent (P = 0.0785) and the polyposis score was lower (P = 0.0702) in the therapy group. Quality of life obviously improved (P = 0.0324), clinical complaints (P = 0.0083) were significantly reduced, and no severe aspirin-related side-effects were observed. CONCLUSION: Aspirin desensitization with a maintenance dose of 100 mg daily has a positive impact on nasal polyp relapse and seems to be a safe and suitable therapy to improve clinical complaints and the quality of life of individuals with AERD.
Subject(s)
Aspirin/administration & dosage , Desensitization, Immunologic , Drug Hypersensitivity/therapy , Respiratory Hypersensitivity/therapy , Adult , Aspirin/adverse effects , Female , Follow-Up Studies , Humans , Male , Middle Aged , Quality of Life , Recurrence , Surveys and Questionnaires , Treatment OutcomeABSTRACT
BACKGROUND Trifunctional antibodies, such as catumaxomab (anti-EpCAM×anti-CD3) and ertumaxomab (anti- HER-2/neu×anti-CD3), transiently link immune effector cells to tumour cells, which results in cellular cytotoxicity towards the tumour cells. A functional immune system is therefore essential for effective anti-tumour activity. However, the commonly observed haematotoxicity of chemotherapeutics and radiation therapy may be associated with some degree of immunosuppression. Combining chemotherapy and trifunctional antibodies in cancer treatment requires understanding of the impact of chemotherapeutics on immune cell function and, thus, on the activity of trifunctional antibodies. METHODS The effect of chemotherapeutic treatment on trifunctional antibody-mediated anti-tumour activity was assessed in vitro. Blood samples were collected from 12 head and neck squamous cell carcinoma patients after chemotherapy (5-fluorouracil, cisplatin) and radiotherapy, and from one healthy control donor. The immune cell status was analysed and mononuclear cells (MNC) were isolated. The potency of catumaxomab and ertumaxomab was assessed in a cytotoxicity assay using MNC isolated from each patient sample in co-culture with a tumour target cell line. The release of infl ammatory cytokines was also monitored in the cell culture supernatant. RESULTS Most patients included in this study had decreased immune cell counts during the course of chemotherapy. Nonetheless, an effective and concentration-dependent anti- tumour activity mediated by trifunctional antibodies was demonstrated using these patient immune effector cells. The immune response activity of the patient immune cells was not impaired one week after cisplatin administration or even three days after the last 5-fluorouracil treatment. CONCLUSION This study shows for the first time that immune effector cells from cancer patients undergoing standard chemotherapy and radiotherapy can be activated by trifunctional antibodies for efficient killing of tumour cells.
Subject(s)
Antibodies, Bispecific/pharmacology , Antibodies, Monoclonal/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/therapy , Aged , Case-Control Studies , Cisplatin/administration & dosage , Cytokines/metabolism , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Survival Rate , Treatment Outcome , Tumor Cells, CulturedABSTRACT
BACKGROUND Trifunctional antibodies, such as catumaxomab (anti-EpCAM×anti-CD3) and ertumaxomab (anti- HER-2/neu×anti-CD3), transiently link immune effector cells to tumour cells, which results in cellular cytotoxicity towards the tumour cells. A functional immune system is therefore essential for effective anti-tumour activity. However, the commonly observed haematotoxicity of chemotherapeutics and radiation therapy may be associated with some degree of immunosuppression. Combining chemotherapy and trifunctional antibodies in cancer treatment requires understanding of the impact of chemotherapeutics on immune cell function and, thus, on the activity of trifunctional antibodies. METHODS The effect of chemotherapeutic treatment on trifunctional antibody-mediated anti-tumour activity was assessed in vitro. Blood samples were collected from 12 head and neck squamous cell carcinoma patients after chemotherapy (5-fluorouracil, cisplatin) and radiotherapy, and from one healthy control donor. The immune cell status was analysed and mononuclear cells (MNC) were isolated. The potency of catumaxomab and ertumaxomab was assessed in a cytotoxicity assay using MNC isolated from each patient sample in co-culture with a tumour target cell line. The release of infl ammatory cytokines was also monitored in the cell culture supernatant. RESULTS Most patients included in this study had decreased immune cell counts during the course of chemotherapy. Nonetheless, an effective and concentration-dependent anti- tumour activity mediated by trifunctional antibodies was demonstrated using these patient immune effector cells. The immune response activity of the patient immune cells was not impaired one week after cisplatin administration or even three days after the last 5-fluorouracil treatment. CONCLUSION This study shows for the first time that immune effector cells from cancer patients undergoing standard chemotherapy and radiotherapy can be activated by trifunctional antibodies for efficient killing of tumour cells (AU)
Subject(s)
Male , Female , Middle Aged , Aged , Humans , Antibodies, Bispecific/pharmacology , Antibodies, Monoclonal/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/therapy , Chemoradiotherapy/methods , Chemoradiotherapy , Case-Control Studies , Cisplatin/administration & dosage , Fluorouracil/administration & dosage , Follow-Up Studies , Neoplasm Staging , Survival Rate , Treatment Outcome , Tumor Cells, Cultured , Cytokines/metabolismABSTRACT
BACKGROUND: Hypopharyngeal stricture can result from a number of causes including chemoradiotherapy and esophagectomy and leads to inability to swallow with aspiration as well as permanent dependence on a gastrostomy tube. Antegrade dilatation or puncture and local mitomycin C application are often unsuccessful and many patients require extensive surgery. METHODS: We report three cases of total hypopharyngeal stenosis with different clinical histories. We present our experience using three modifications of the combined anterograde-retrograde endoscopic technique with resection of the stenosis by laser technique under diaphanoscopic control. RESULTS: In all cases the hypopharyngeal-esophageal passage was restored. No complications occurred as a result of the procedure. CONCLUSION: Combined direct hypopharyngoscopy with retrograde esophagoscopy represents a viable alternative to more extensive approaches for recanalization of selected obstructing hypopharyngeal stenoses when antegrade identification of the esophageal entrance fails.
