New Treatments for Prostate Cancer Are in the Pipeline

NEW YORK--Pharmaceutical companies are currently investigating25 new treatments for prostate cancer, including a potential vaccine,Alan Holmer, president of the Pharmaceutical Research and Manufacturersof America, said at a media briefing conducted by the AmericanCancer Society and the New York City-based Cancer Research Institute.

Along with new agents in the pipeline for prostate cancer arenew applications and different formulations of older drugs, saidmedical oncologist Gene Resnick, MD, vice president for clinicalresearch, Schering-Plough Research Institute.

A new use of existing agents is the combination of flutamide (Eulexin)and a luteinizing hormone-releasing hormone agonist (LHRH-A) inearly-stage prostate cancer. In another approach, flu-tamide plusfinasteride (Proscar) is being studied for use in advanced orrecurrent prostate cancer.

Established chemotherapeutic agents are also being studied innew applications and combinations; for example, mitoxantrone (Novantrone)in combination with prednisone for palliation of advanced hormone-refractoryprostate cancer (see also page 4); fluorouracil with cisplatin(Platinol) in refractory metastatic disease; and flutamide withepiru-bicin in advanced prostate cancer.

A new liposomal form of doxorubicin is in development, and otherliposomal products are in the works, he said, as are potentiallymore effective hormonal agents, including new LHRH antagonistsand agonists, new antiandrogens, and other investigational drugssuch as liarozole and the synthetic retinoid fenretinide.

Dr. Resnick is particularly excited by efforts to develop biologicalresponse modifiers and gene therapy techniques for use in prostateand other cancers. For example, a signal transduction inhibitorbeing developed at the National Cancer Institute changes the calciumflow in each cell and may have some application in prostate cancer.

Advances in Radiotherapy

Three-dimensional conformal radiotherapy (3D-CRT) is now increasinglysophisticated and better able to precisely target prostate tumorsto minimize toxicity, Zvi Fuks, MD, said at the briefing. Dr.Fuks is chairman of the Department of Radiation Oncology, MemorialSloan-Kettering Cancer Center.

The multifield 3D-CRT approach uses "powerful computers andnew mathematical algorithms to reconstruct the prostate on thecomputer," he said. Each field is selected to focus maximallyon the prostate, and the radiation beam conforms to the shapeof the prostate, avoiding as much as possible the surroundingnormal tissues.

Another new computer technique, the inverse approach to 3D-CRTtreatment planning, which has been used on about a dozen patientsso far at Sloan-Kettering, holds the promise of providing expertconformal radiotherapy planning to hospitals and cancer centersthat could not otherwise provide such treatment, Dr. Fuks said.

Using the inverse approach, radiologists enter the patient's anatomicaldata into the computer and tell the computer to provide a desireddose distribution to the prostate and normal tissues. The computergenerates an "optimized program" that provides instructionsfor the treatment machine.

"The program could be made available to every facility andevery patient in the United States," Dr. Fuks said, thusreducing the need for 3D-CRT experts, who are currently in shortsupply.

Another useful technique in early-stage prostate cancer is seedimplantation, which has now been refined so that there is no longera need to restrict dosages to avoid rectal or bladder intolerance,he said.

With the help of computers, radiotherapy seeds are implanted sothat they conform closely to the shape of the prostate (anotherform of conformal therapy), thereby keeping the radiation as muchas possible within the prostate. This technique is "expertdependent," Dr. Fuks said, requiring "pre-planning,or else you may miss part of the tumor."

Immunotherapy Techniques

Immunotherapy techniques involving monoclonal antibodies (MoAbs)are the focus of work by Neil H. Bander, MD, director of urologiconcology, New York Hospital-Cornell Medical Center. His grouphas just received FDA approval to begin clinical trials of a MoAb-radioisotopeconjugate for prostate cancer, he said at the briefing.

A team led by Howard Scher, MD, chief of the genitourinary oncologyservice at Sloan-Kettering, is now working on a series of phaseI/II clinical trials using conjugate vaccines directed againstcell surface antigens expressed on prostate cancer cells--a promisingapproach, he explained, because prostate tumors display a numberof well-identified marker antigens on their surface, includingprostate-specific antigen (PSA).

Four Vaccines Under Development

The Memorial Sloan-Kettering research group is developing fourdifferent polyvalent vaccines, one of which they hope will beuseful in preventing the development of prostate cancer in menwith elevated PSA levels but no clinically detectable disease.

In other studies, Dr. Scher's team has found that prostate tumorsthat show androgen-independent progression are associated withthe activation of certain tyrosine kinase growth factor receptors.Inhibiting this pathway with an antibody was shown to "cure"laboratory mice with such tumors, and phase I/II trials of thistechnique may soon be initiated in prostate cancer patients.