There will be 30,000 deaths due to prostatic cancer in the United States this year. Besides a high annual mortality rate, prostatic cancer also has a high incidence rate, accounting for 22 percent of the total annual incidence for all forms of cancer in males in the U.S. Both the annual incidence and mortality rates have increased steadily since the 1930's to the present time. In 1990, prostatic cancer became the most commonly diagnosed cancer in the American male. Nearly all men with metastatic prostatic cancer treated by androgen ablation have an initial beneficial response to such therapy. Unfortunately, essentially all treated patients relapse to an androgen-insensitive state in which additional forms of antiandrogen therapy are ineffective no matter how aggressively given. Because of the relapse phenomenon, the annual death rate from prostatic cancer has not decreased at all over the subsequent 50 years since androgen ablation has been standard therapy for this disorder. Over the last fifty years, the superficially benign nature of androgen ablation has tended to disguise the fact that metastatic prostatic cancer is still a fatal disease for which no therapy is available which effectively increases survival. New approaches to this devastating disease are urgently needed. In this application, the usefulness of a quinoline 3-carboxide (ie linomide) in preventing the development and progression of prostatic cancer will be tested in vivo. These studies are based upon the newly identified ability of linomide to inhibit the angiogenic response in prostatic cancers in vivo. These studies are critical in determining objectively the most appropriate time during the progression of prostate cancer to use linomide treatment alone or in combination with other agents. The preclinical data generated will form the basis for rational decision concerning whether human trials for chemoprevention of prostatic cancer should be performed with linomide.
