Good drug, bad luck: business, regulatory issues can create obstacles for drug development.

Anybody involved with cancer knows that bad things happen to good people. Sometimes bad things happen to good cancer drugs, too, for reasons ranging from regulatory red tape to intellectual property constraints. The stories of two drugs—one an oral chemotherapy, the other a bone-seeking radiopharmaceutical—show how regulatory or licensing barriers can block a promising compound's path. At the annual meeting of the Ameri-can Society for Clinical Oncology (ASCO) in June 2004, Norman Wolmark, M.D., had good news: results from a large trial of several years' duration, in which an oral chemo-therapy drug called UFT (uracil/tegafur) was tested in some 1,600 patients with colorectal cancer whose primary tumors had been removed. Wolmark, chairman of the Department of Human Oncology Allegheny General Hospital in Pitts-burgh and the study's lead investigator, reported that an oral regimen of UFT plus another drug, leucovorin, was as effective as the existing standard treatment—intravenous 5-fluorouracil plus leucovorin (5-FU/LV)—when the trials were begun in 1997. The two regimens were about equally toxic. Given the advantage of taking a pill at home instead of visiting the doctor 30 times for an intravenous infusion, the trial's results should have left Wolmark ecstatic. Instead, he wryly announced to his audience at the ASCO meeting that they might just as well forget about his trial's results. UFT was not available, nor likely to be. Despite its use in many other parts of the world—and despite a unanimous September 1999 recommendation for approval given by the Oncology Drug Approval Committee (ODAC), the group of outside experts the U.S. Food and Administration (FDA) tasks with evaluating cancer drug applications— UFT was effectively quashed by the FDA. Sponsor Bristol-Myers Squibb (BMS) withdrew its application in March 2000 to avoid certain rejection and has made no further effort to get marketing approval for UFT in the United States. The UFT story was covered extensively in the newsletter The Cancer Letter as it broke, and its implications carry forward to the present. " Had we known that this drug wouldn't be available, we wouldn't have started this trial, " said Wolmark. " Why subject patients to a regimen that won't be available? " BMS filed for FDA approval in 1999 on the strength of two pivotal studies— one of them the largest yet conducted in metastatic colorectal cancer—of an oral UFT/LV regimen. In these trials, UFT proved roughly equivalent to 5-FU/LV, and less toxic. But the FDA …