Biomedical subjects

Dominique Tschudi

Publications and source records attributed to Dominique Tschudi.

2 recordsLinked to original sources

PubMed2003

Quality of life after different treatment modalities for carcinoma of the oropharynx.

OBJECTIVES: To assess the long-term posttreatment quality of life of patients with carcinoma of the oropharynx treated with different treatment modalities. STUDY DESIGN: Retrospective chart review and patient response to EORTC quality of life core questionnaire QLQ-C30 and EORTC quality of life core head and neck cancer module QLQ-H&N35 questionnaires. METHODS: Two hundred and seventeen patients with carcinoma of the oropharynx were treated with curative intent between 1990 and 1998. In January 2001, a total of 111 disease-free survivors were identified and included in this study. The questionnaires were completed by 99 patients (89% completion rate). RESULTS: Of 99 patients, 31 patients were treated with surgery alone, 19 with radiation therapy alone and 49 with surgery followed by postoperative irradiation. Median follow-up for the entire study group was 71 months. Physical, role, emotional, cognitive and social functioning reflected in the functional scale scores of the global EORTC QLQ-C30 were generally good and showed no significant differences for the different treatment modalities. Comparison of the head and neck specific EORTC QLQ-H&N35 scores revealed significantly less troubles with swallowing (P = 0.006), social eating (P = 0.007) and social contact (P = 0.008), dry mouth (P < 0.0001), sticky saliva (P = 0.0001) and mouth opening (P = 0.001) in non-irradiated patients versus those treated with any either primary or postoperative radiation therapy. Patients undergoing surgery (with and without postoperative irradiation) had less pain (P = 0.04), less problems with social eating (P = 0.009) and less restricted mouth opening (P = 0.03) than the nonsurgically treated patients. CONCLUSIONS: Quality of life after curative treatment of oropharyngeal carcinoma is generally good. Differences regarding quality of life between the different treatment modalities manifest themselves in the head and neck specific EORTC QLQ-H&N35 module, not in the global core questionnaire EORTC QLQ-C30.

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PubMed2003

A recombinant immunotoxin derived from a humanized epithelial cell adhesion molecule-specific single-chain antibody fragment has potent and selective antitumor activity.

PURPOSE: Epithelial cell adhesion molecule (Ep-CAM) is a tumor-associated antigen overexpressed in many solid tumors but shows limited expression in normal epithelial tissues. To exploit this favorable expression pattern for targeted cancer therapy, an Ep-CAM-specific recombinant immunotoxin was developed and its antitumor activity investigated. EXPERIMENTAL DESIGN: The immunotoxin 4D5MOCB-ETA was developed by genetically fusing a truncated form of Pseudomonas aeruginosa exotoxin A (ETA) (ETA(252-608)KDEL) to the highly stable humanized single-chain antibody fragment (scFv) 4D5MOCB. Cytotoxicity of 4D5MOCB-ETA was measured in cell growth and leucine incorporation assays in vitro. Tumor localization and antitumor activity were assessed in athymic mice bearing established human tumor xenografts. RESULTS: Fusion of the toxin moiety to the scFv did neither affect its thermal stability nor its antigen-binding affinity. In vitro, 4D5MOCB-ETA potently and specifically inhibited protein synthesis and reduced the viability of Ep-CAM-positive carcinoma cells of diverse histological origins with IC(50)s ranging from 0.005 to 0.2 pM. Upon systemic administration in mice, 4D5MOCB-ETA showed similar organ distribution as the scFv 4D5MOCB and preferentially localized to Ep-CAM-positive tumor xenografts with a tumor:blood ratio of 5.4. The potent antitumor activity of 4D5MOCB-ETA was demonstrated by its ability to strongly inhibit the growth and induce regression of relatively large tumor xenografts derived from lung, colon, or squamous cell carcinomas. CONCLUSIONS: We describe for the first time the development of a fully recombinant Ep-CAM-specific immunotoxin and demonstrate its potent activity against solid tumors of various histological origins. 4D5MOCB-ETA is currently being evaluated in a Phase I study in patients with refractory squamous cell carcinoma of the head and neck.

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