Phase I Success for new Prostate Cancer Drug

Monomethyl auristatin E MMAE with a targeting antibody may help direct medications to cancer cells

(RxWiki News) For men with aggressive prostate cancer, few treatment options are available. A new drug, however, showed a positive effect in reducing the number of tumor cells and cancer markers in advanced prostate cancer.

Scientists recently developed a drug that zeroes in on a protein found on the surface of prostate cancer cells. When the cells absorb the drug, a cancer-killing agent is released.

This means a new therapy may help later-stage prostate cancer patients.

"Ask your oncologist about new therapies. "

Daniel Petrylak, MD, current director of the Prostate Cancer Program/Genitourinary Cancer Program and co-director of the Signal Transduction Program at Yale University Medical Center, and his fellow scientists recruited 50 prostate cancer patients for this study.

The patients had the most advanced form of the disease—it had spread to the bones and organs. The subjects had received up to two prior chemotherapies and hormone therapy, but the cancer was still progressing.

Dr. Petrylak and his colleagues developed a medication that combined a cancer-destroying drug called monomethyl auristatin E (MMAE) with a targeting antibody that would help direct the medication to the cancer cells.

The antibody targets a protein on the cancer cells called prostate specific membrane antigen (PSMA). MMAE disrupts tubulins, the tiny molecules inside a cell that are essential for cell division. This combination of the antibody and the drug is called a PSMA antibody drug conjugate (PSMA ADC).

“By conjugating the antibody with a chemotherapeutic agent, we hoped that this would lead to more targeted therapy, which would have fewer toxic side effects and would be more effective against the cancer,” said Dr. Petrylak.

The new drug was administered in three-week cycles for up to four treatment cycles. About half of the patients who received doses of at least 1.8 mg of the drug displayed signs of anti-tumor activity. They had either a 50 percent or greater reduction in PSA levels or a fall in circulating tumor cells (CTC) in the blood to less than five cells per 7.5 ml of blood, or both.

PSA is prostate-specific antigen, a protein produced by the prostate gland. The higher a man’s PSA level is in a blood test, the more likely it is that he has prostate cancer, according to the National Cancer Institute. Patients had little adverse affect from the drug. At the highest dose of 2.8 mg, patients experience neutropenia—a decrease in the number of white blood cells. One patient died, but scientists are unsure of the cause of death.

“These results show PSMA ADC has anti-tumor activity in patients who have failed [prior therapy],” said Dr. Petrylak. "The fact that this new targeted therapy is active against the most advanced forms of prostate cancer is encouraging, as few or no therapeutic options are available at present."

Amy Martini, a spokesperson from Progenics Pharmaceuticals, the company that funded the study, told dailyRx News that it initiated a phase II clinical study of this drug with up to 75 patients in late September. The recommended dose for these patients is 2.5 mg. This new trial is evaluating responses in PSA and CTC. Investigators are also examining control of the cancer spread to the bone, internal organs and lymph nodes.

“Given its stage of development, it is still premature to estimate potential pricing for this potential therapy,” Martini said.

The study was presented in November at the 24th European Organization for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland. The study was funded by Progenics Pharmaceuticals Inc. All research is considered preliminary before it’s published in a peer-reviewed journal.

Review Date: 
November 28, 2012