Oral cancer chemotherapy in paediatric patients: obstacles and potential for development and utilisation.

Although most cancer chemotherapy in children is administered parenterally, oral formulations are becoming increasingly available for use in patients as young as infants. Incentives for this approach include safety, flexibility, reduced financial cost, improved quality of life, and the potential for improved efficacy. The ability to deliver chemotherapy at home and apply schedules of administration that increase the agent's efficacy because patients do not require hospitalisation or visits to the clinic renders oral chemotherapy particularly attractive. Obstacles to oral chemotherapy in paediatric patients include restrictions in dose size and schedule, uncertain or low bioavailability, adverse effects of malabsorption, and adherence (noncompliance and refusal to take oral chemotherapy). Techniques to overcome most of these limitations are available or can be developed, and lack of an oral formulation can be solved in many instances by the pharmaceutical industry. Future developments in oral chemotherapy should not be limited to adult patient applications.

The effects of antiepileptic drugs on estrogen-induced electrographic spike-wave discharge.

In locally anesthetized, paralyzed cats with bilateral conjugated estrogen (CE)-induced foci in sensory motor cortex, electrographic activity was characterized by 2 to 3 Hz spike and slow wave discharge. Commonly used anti-petit mal drugs (esthosuximide, trimethadione, acetazolamide and diazepam) all reduced CE-induced spike wave activity while diphenylhydantoin converted such activity into 9 to 12 Hz polyspike bursts separated by periods of interictal silence. Correlation appears to exist, therefore, between the ability of the drug to reduce CE-induced spike wave activity and its clinical utility in petit mal epilepsy. In addition to the above compounds, five drugs of less proven utility were evaluated. Of these, two benzodiazepine derivatives (clonazepam and clorazepate) were found to exert a potent and prolonged depressant action on CE-induced activity. The relation of CE to clinical petit mal epilepsy and the potential usefulness of CE as a laboratory model for the evaluation of anti-petit mal drugs are discussed.