ROCKVILLE, Md. _ An FDA advisory panel recommendedOrganon Teknika Corp.'s TICE (BCG) preparation for approval totreat recurrent papillary bladder cancer. Despite contradictory clinicalresults, the committee voted 9-to-1 with one abstention torecommend the immunotherapy as a topical treatment for these highrisk bladder cancers.
"This recommendation means that patient's are going to be kept aliveand disease-free longer," said Michael Hanna, CEO of PerImmune,in Rockville, which did the clinical work for Organon, of Durham,N.C. "Some may even avoid the removal of their bladders."
In 1989, TICE (BCG) was approved for carcinoma in situ of thebladder _ a cancer that coats the bladder and cannot be treatedsurgically without complete removal of the bladder. Organon isseeking marketing approval for the product in recurrence of high-grade papillary cancer which forms distinct foci in the bladder.
Bacillus Calmette Guerin (BCG) comes from the earliest attempts todevelop a vaccine that would protect against tuberculosis. It is anactive but attenuated bovine mycobacteria. Many countriesworldwide employ BCG to protect against tuberculosis, however ithas not been approved for that purpose in the U.S.
In the early 1970's, scientists began to recognize that BCG hadanticancer properties. In the 1980s Organon began to explore theTICE strain of the infectious agent as a topical instillation into thebladder to treat cancer. "Many people think that BCG simply causesinflammation in the bladder that attacks the cancer, but inflammationis associated with cancer," said Donald Lamm, a professor of urologyat the University of West Virginia in Morgantown, who participatedin the clinical trials of TICE. "Instead, BCG is activating aninflammatory response that releases cancer-fighting cytokines."
Organon presented data from two published clinical trials of TICE intreating recurrent and high grade papillary bladder cancer. The firststudy of 469 patients with bladder cancer in The Netherlandscompared
TICE with another BCG preparation RIVM and mitomycin C (MMC_ chemotherapy agent). Forty-four percent of the patients receivingTICE had recurrences of their cancers whereas 34 percent of theRIVM (BCG) treated group had recurrences and only 29 percent ofthose getting MMC developed a recurrence of their cancers. Thecommittee agreed unanimously that these results did NOT support arecommendation for approval.
However, the company also presented the results of a multicenterstudy conducted in the U.S. by the Southwest Oncology Group. Thisstudy treated 469 patients with either TICE or MMC. Forty-sixpercent of the patients receiving TICE died or had a recurrence oftheir cancer while 57 percent of those receiving MMC had arecurrence or died. TICE therapy was associated with serious sideeffects which included fever, blood infections and inflammation ofthe genital tract that resulted in orchiectomy. Side effects occurredthree times more often in males than females.
"The therapy is not innocuous," Lamm said. "However, most of theadverse events can be treated."
The panel, however, was swayed by the U.S. data and voted forapproval. "It is fairly easy to see that the SWOG data providesevidence that TICE BCG is effective," said panel member DerekRaghavan chief of investigational therapeutics at Roswell ParkCancer Institute in Buffalo, N.Y.
Richard Gelber, a biostatistician at the Dana Farber Cancer Institute,in Boston, disagreed, "There simply isn't enough data to say whetherthis product is effective."
The FDA usually follows the recommendations of its advisory panelsbut is under no obligation to do so.
Should Organon gain approval for TICE it will likely see competitionfrom Connaught Laboratories Ltd., of North York, Canada, which isdeveloping its own BCG product for bladder cancer. n
-- Lisa Seachrist Washington Editor
(c) 1997 American Health Consultants. All rights reserved.