Predictive value of p53, Bcl2 and bax in the radiotherapy of head and neck cancer.

Radiation is known to induce DNA damage resulting in the onset of apoptosis. The apoptosis is modulated by p53, Bcl2 and Bax proteins. High level of wild type p53 is required for radiation induced apoptosis. The p53 status, therefore, may be a crucial determinant of radiosensitivity of tumor cells. Overexpression of Bcl2, however, inhibits apoptosis via hetero- and homodimeric interaction. Bax might function as a cell death effector molecule that is neutralized by Bcl2. The aim of the present study is to investigate the correlation between p53, Bcl2, Bax and c-myc levels and the clinical response of head and neck cancer patients to radiation. The base line and 30 GY gamma radiation induced values of p53, Bcl2, Bax and c-myc were estimated by Western blot in 40 biopsies of head and neck cancers. We found that the radiosensitivity of head and neck cancer patients depends on the ratio of p53, Bcl2 and Bax protein levels. High Bcl2 levels resulted in radioresistance of cancer patients. Overexpression of Bax and c-myc may ensure the radiosensitivity of head and neck cancer patients. Our studies indicate that prediction of radiation sensitivity of tumors could be based on the simultaneous evaluation of p53, Bax and Bcl2 levels.

[Low-dose Taxol radiosensitization in locally advanced head and neck cancers] / Alacsony dózisú Taxol-sugárérzékenyítés helyileg elôrehaladott fej-nyaki daganatokban.

INTRODUCTION: Combined modality treatment with chemotherapy and radiotherapy in locally advanced head and neck cancers is an effective and often the only treatment with a chance of cure. An alternative is to use chemotherapeutic agents at low doses as radiosensitizers. In this study we examined the radiosensitizing effect of low dose Taxol in locally advanced head and neck cancer. Patients and methods: 26 patients with locally advanced squamous cell carcinoma of the oral cavity and the oropharynx were treated with external beam radiotherapy up to doses of 66-70 Gy and received concomitantly 2 mg/m(2) Taxol intravenously three times a week. Response rates according to WHO criteria, side effects according to the National Cancer Institute Common Toxicity Criteria, overall and progression-free survival were evaluated. RESULTS: All patients completed the therapy. Median radiation dose was 66 Gy, Taxol dose 40 mg/m(2) and treatment duration 54 days. 8 weeks after completion of therapy complete response was 30.8%, partial response 34.6%, stable disease 11.5% and progressive disease 23.1%. The median follow-up time was 25 months (9-36). At the cloes- out date 12 (46,1%) of the patients were alive, 9 without evidence of disease. The estimated median overall survival was 22 months (CI 14.2-34.6), the median progression-free survival 12 months (CI 5.2-18.8). We observed four grade 4, fourteen grade 3 and numerous grade 1-2 side effects. There was no treatment related death. DISCUSSION: Our regimen resulted in a worse response rate than the aggressive chemoradiation protocols treating the same disease. However, the two-year survival was comparable with the results of other studies. The advantages of our schedule are that it is well tolerated, easy to perform on an outpatient basis, resource effective and does not deteriorate the general condition of the patients, therefore successive therapy can be carried out immediately if necessary. We intend to evaluate the effectivity of this treatment in a study comparing radiotherapy with Taxol sensitization versus radiotherapy alone.

[Combined modality treatment of locally advanced oral and oropharyngeal cancer following primary radiotherapy with and without taxol radiosenzitization] / Komplex onkoterápia eredményei elôrehaladott stádiumú fej-nyaki laphámrákos betegek Taxol-sugárérzékenyítéssel és anélkül végzett primer sugárkezelését követôen.

AIM: To determine the effect of radiosensitization with Taxol and multimodality treatments on the survival of advanced oral and oropharyngeal cancer. Patients, methods: 56 patients with St. III-IV oral or oropharyngeal cancer were treated with external beam radiotherapy; 26 of them were sensitized by low-dose paxlitaxel and 30 were irradiated traditionally. The median follow up was 23 months (17-36). Endpoints of the study were: response to radiotherapy, progression-free and overall survival and the results of surgery and chemotherapy following radiation. RESULTS: 73.3% (41/56) of treatments resulted in CR or PR with median 10 months (0-33) progression-free and 14 months (4-33) overall survival. There was no significant difference between the radiosensitized and traditional radiotherapy group (p=0.6). The survival was significantly influenced by the stage of tumor and the response to primary radiotherapy. Seven (38.9%) of 16 patients treated also by either surgery or chemotherapy for recurrent or residual disease are free of cancer, 6 (35%) alive with tumor and 5 (26.1%) died with median survivals of 21, 20.5 and 18 months, respectively. Those treated only with radiotherapy with or without sensitization are free of cancer in 31.6%, alive with cancer 5.3%, died 63.2%. CONCLUSION: There were significant correlation between tumor stage, response to radiotherapy and combined modality treatment, and surival. The radiosensitizing effect of Taxol was not obvious so far, it may be apparent in the future by analyzing the long term survival data.