We are pleased that the articles [1, 2] reporting the results of two multicenter, placebo-controlled trials on the effect of megestrol acetate in patients with AIDS-related cachexia generated several thoughtful letters.

The comments of Drs. Hengge and associates and Dr. Cook about alternative drug therapies (oxymetholone and prednisone) for AIDS-related cachexia are intriguing. With regard to prednisone, the anecdotal report of "dramatic weight gain and increased appetite" is surprising because prednisone treatment of cancer-related anorexia and cachexia has not resulted in a sustained increase in food intake or significant improvement in weight [3, 4]. We eagerly await a peer-reviewed report of the studies of oxymetholone and prednisone so that comparisons of efficacy, not merely cost, can be made between these agents and megestrol acetate.

Drs. Hengge and associates and Dr. Cohen express concern that megestrol acetate does not appear to improve function or survival. As stated in our reports, the median survival of patients receiving megestrol was equivalent to or greater than the median survival of patients receiving placebo. In any discussion of longevity, it is important to restate that megestrol treatment substantially improved quality-of-life measures. For terminally ill patients, this enhanced sense of well-being is a significant treatment benefit.

Dr. Maurer's observation of adrenal insufficiency is of concern. On the basis of our experience, this complication is not commonly associated with megestrol therapy. As mentioned, one study patient developed Cushingoid characteristics, which suggests a glucocorticoid effect by megestrol. We recommend that future megestrol and other steroid hormone studies include careful measurement of adrenal function and regulation.

We disagree with Dr. Cohen's hypothesis that cachexia is a beneficial host defense. In AIDS and many other diseases, nutritional status is well correlated with survival [5].

Finally, with respect to the price of megestrol treatment, we concur that costs of approximately $363 and $726 for 12 weeks of therapy (400 and 800 mg/d, respectively) are significant. Less expensive, equally effective, and well-tolerated alternatives are needed.

We anticipate that interest in AIDS-related cachexia will be stimulated by these two reports on megestrol acetate. The studies clearly show that megestrol significantly increases appetite, body weight, and sense of well-being in cachectic patients with AIDS. In the absence of other Food and Drug Administration (FDA)-approved therapies for weight gain in the AIDS wasting syndrome, these results should not be minimized. We await the discovery of additional efficacious therapies. Until then, megestrol and marinol remain the only FDA-approved drugs.