Programmed cell death as a prognostic indicator for radiation therapy in cervical carcinoma patients: a pilot study.

PURPOSE: In clinical practice, radiation therapy often fails in cervical carcinoma stage IIIB and there is a need to develop a predictive assay for prognosis of radiation treatment outcome in cancer patient. We have attempted to evaluate the relevance of changes in Membrane Fluidity (MF) and associated apoptotic cell death in cervical cancer cells after first fractionated dose of radiation therapy to treatment outcome of stage IIIB cervical carcinoma patients. MATERIALS AND METHODS: Biopsies of 15 patients with histologically proven cervix cancer were collected from the patients before and 24 h after first fractionated radiation dose of 2 grays (Gy). Cell suspension made in Dulbecco's Modified Eagle's Medium (DMEM) were used for further investigations and cell suspension of cervix cancer patient were used to measure MF by fluorescence polarization method and apoptotic index (AI) was determined by Tdt dUTP Nucleotide End Labeling (TUNEL) assay. RESULTS: A substantial increase in MF and AI was observed in cervical cancer cells irradiated ex vivo . A significant correlation ( P P > 0.1) was detected between changes in MF and treatment outcome of patients. CONCLUSION: Preliminary results showed significant change in MF and a marked increase in percentage apoptosis of cervix cancer cells irradiated ex vivo . The changes in AI after first fractionated dose of radiotherapy in cervical carcinoma patients may provide a predictor of prognosis for radiotherapy in uterine cervical carcinoma patients.

A phase I trial of tocoferol monoglucoside in patients undergoing hemi-body radiation.

PURPOSE: To evaluate Tocoferol monoglucoside (TMG), a water soluble vit. E. in a phase I trial, as a radiation protector in those undergoing hemi-body radiation for disseminated disease. MATERIALS AND METHODS: Patients scheduled to receive modified hemi-body radiation were accrued for the study. Patients not only had disseminated skeletal disease but, were heavily pretreated Seven patients were accrued for the study. Patients received 1 and 2 gms of TMG. 30-40 minutes before hemibody radiation. A dose of 600 cGy was delivered on telecobalt equipment at mid plane. Immediate Toxicities were evaluated as well as response to pain. RESULTS: All the seven patients underwent radiation uneventfully. There was no drug related toxicity. Pain relief was adequate. CONCLUSION: Tocoferol monoglucoside an effective antioxidant with no significant acute toxicity, when administered in a dose of 1 or 2 gms per oral route. TMG being water-soluble can have global antioxidant and radio protective effects. This needs further clinical evaluation.

A clinical study to assess chlorpromazine as hypoxic cell sensitizer in head & neck cancer treated with conventional radiation.

A randomized prospective study was conducted to evaluate the effectiveness of chlorpromazine as a sensitizer of radiation in advanced head and neck cancers. Patients with unresectable laryngopharyngeal cancers except glottic cancers, with histologically proven squamous cell carcinoma staged III and IV were accrued for the study. Patients received radiation to a total dose of 6000 cGy in six weeks in both the groups except that patients in the study group received 50 mgs Chlorpromazine (CPZ) in divided doses. Fourteen of 20 patients showed complete response in the control group whereas 34 of 38 patients in chlorpromazine treated group had complete regression of the tumour (p = 0.016). The survival was (p = 0.08) better in patients receiving CPZ. This preliminary study shows beneficial effects of chlorpromazine. No adverse effects due to chlorpromazine in conjunction with radiation were documented.

Assessment of chlorpromazine as radiation sensitizer and protector.

In vitro studies of chlorpromazine (CPZ) a popular anti-psychotic drug has shown radiation sensitizing effects at higher celluar concentration and protective effect at a lower concentration. The present study was designed to evaluate both sensitizing and protective effects in the treatment of advanced cancer of the cervix treated with hypofractionated external radiation and intratumoural injection of chlopromazine. Twenty patients were treated with intratumoural CPZ and radiation, while, 23 patients received radiation alone. A 52.94% complete response was noted in CPZ arm while 39.1% complete response in the control. A trend towards improved response is seen in CPZ group. Similarly patients who received CPZ showed significantly low proctitis rates.

Capillary perfusion--a study in two groups of radiated patients for cancer of head and neck.

Laser Doppler velocitometry is novel non-invasive technique to assess cutaneous microcirculation. Patients undergoing radiation therapy for head and neck cancer with convention and accelerated fraction action were evaluated under normal condition before and after radiation. A total of 70 sites in group A (conventional fractionation) and 35 sites in group B (accelerated fractionation were evaluated. Increase in perfusion was noted in patients undergoing radiation with accelerated fractionation.