This paper looks at a new approach to the design and analysis of Phase 1 clinical trials in cancer. The basic idea and motivation behind the approach stem from an attempt to reconcile the needs of dose-finding experimentation with the ethical demands of established medical practice. It is argued that for these trials the particular shape of the dose toxicity curve is of little interest. Attention focuses rather on identifying a dose with a given targeted toxicity level and on concentrating experimentation at that which all current available evidence indicates to be the best estimate of this level. Such an approach not only makes an explicit attempt to meet ethical requirements but also enables the use of models whose only requirements are that locally (i.e., around the dose corresponding to the targeted toxicity level) they reasonably well approximate the true probability of toxic response. Although a large number of models could be contemplated, we look at a particularly simple one. Extensive simulations show the model to have real promise.

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Veno-occlusive disease, which developed in 54% of bone marrow transplant recipients, is frequently associated with renal and cardiopulmonary failure. Pretransplant transaminase elevations, use of high-dose cytoreductive therapy, and persistent fever during cytoreductive therapy are independent predictors of severe VOD.

To examine the clinical and historical features and the natural history of aneurysmal coronary disease, we reviewed the registry data of the Coronary Artery Surgery Study (CASS). Nine hundred seventy-eight patients, representing 4.9% of the total registry population, were identified as having aneurysmal disease. No significant differences were noted between aneurysmal and nonaneurysmal coronary disease patients when features such as hypertension, diabetes, lipid abnormalities, family history, cigarette consumption, incidence of documented myocardial infarction, presence and severity of angina, and presence of peripheral vascular disease were examined. In addition, no difference in 5-year medical survival was noted between these two groups. These findings suggest that aneurysmal coronary disease does not represent a distinct clinical entity but is, rather, a variant of coronary atherosclerosis.