Toxicity after cervical cancer treatment using radiotherapy and chemotherapy.

The increasing concern at toxicity rates after radiotherapy and concomitant cytotoxic chemotherapy has prompted this viewpoint of basic scientific mechanisms. Toxicity is a function of many controllable treatment-related variables: external beam technique; dose and fractionation; brachytherapy volume, dose and dose rate; and chemotherapy sensitisation of normal tissues. To obtain optimal results, detailed attention must be given to all these factors. For chemotherapy-related toxicity, a hypothesis is suggested for testing in clinical trials: the use of chemotherapy immediately before radiotherapy may sensitise normal tissues to a much greater extent than if given a few hours later, when platinum will no longer be in an ionised state, but will be protein bound. It may also be preferable to use the platinum after all radiotherapy exposures each week, in order to prevent compounding of incomplete repair of sublethal DNA damage and reduce its conversion into lethal damage. Because the dose intensity of the platinum schedules is as high as in ovarian cancer, it is assumed that the action on tumour cells is independent cell kill, so that the temporal pattern of administration will not be as important. Further analysis of patients treated at the Clatterbridge and Hammersmith hospitals is suggested, because of the low level of serious morbidity found there using different approaches, including the above chemotherapy scheduling. A better national approach to the treatment and study of cervix cancer is indicated, with quality of life as an important outcome measure, as well as survival