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Cerebral metastases are a common problem in patients with small cell lung cancer, with a crude incidence of approximately 25%. However, a review of the published data shows that, in patients who achieve a complete response with chemotherapy, the incidence of cerebral metastasis as the first or only site of treatment failure is approximately 14%. This is the proportion of patients who might be expected to obtain a survival benefit if their cerebral metastases could have been prevented. The incidence of cerebral metastases varies with the length of survival and the administration of prophylactic cranial irradiation (PCI). The incidencee may also be influenced by the administration of systemic chemotherapy and the timing of thoracic irradiation (in patients with limited disease). PCI has been shown in randomized trials to reduce the crude incidence of cerebral metastases to 7%, but this has not resulted in a detectable survival advantage, possibly because the numbers of randomized patients in complete response have been too small. Numerous retrospective studies now link PCI with late neurotoxicity, with an overall crude incidence of approximately 19%, but with considerable variation from study to study, ranging from less than 10% to over 80%. This toxicity may have been reduced if small doses per fraction had been used, and chemotherapy had not been given concurrently with PCI. Because of these concerns about late toxicity and the small proportion of patients who might obtain a survival benefit from PCI, it is not possible to recommend it as a routine treatment at this time. Nevertheless, the treatment of established cerebral metastases is unsatisfactory, with complete response to radiotherapy in the range 20% to 30% and median survivals of 4 months or less. Because cerebral metastasis is likely to become an increasing cause of primary failure as patients survive longer, further studies should aim to define an optimum dose/fractionation schedule for PCI, and also evaluate its effect not only on survival and neurotoxicity, but also any benefits resulting from a reduction in morbidity resulting from the development of cerebral metastases.

The pressor response to angiotensin II was measured in unanesthetized, chronically catheterized pregnant and nonpregnant rabbits. Angiotensin II was infused intravenously for 10 minutes at a dose of 50 and 124 ng/kg/min. No difference in control mean arterial blood pressure was observed between pregnant and nonpregnant rabbits. The pressure change in response to angiotensin II was significantly greater in nonpregnant rabbits than in pregnant rabbits (P < 0.002). Plasma samples were analyzed for angiotensin II concentration by radioimmunoassay. The results showed that there was no difference in plasma angiotensin II concentration between pregnant and nonpregnant rabbits following angiotensin II infusions. In a separate series we observed the effect of 5 mg of phenoxybenzamine on the pressor response to angiotensin II. After phenoxybenzamine treatment the control mean arterial blood pressure was significantly greater in nonpregnant rabbits than in pregnant rabbits, but the change in pressure in response to angiotensin II in nonpregnant rabbits was not significantly different from that of pregnant rabbits. These results show (1) that pregnant rabbits have a decreased sensitivity to angiotensin II, (2) that this decreased sensitivity is not due to differences in plasma concentration of angiotensin II, and (3) that this differential sensitivity to angiotensin II can be prevented by alpha-receptor blockade.