Nose Drop Drug Helps Fight AIDS-Related Cancer

This is the first treatment aimed at disrupting the production of new blood vessels to be successful against the most common malignancy associated with the human immunodeficiency virus, for which there is currently no cure.

A total of 44 patients -- 42 men and 2 women -- with KS were enrolled in an open-label Phase I/II trial of IM862, a tiny protein normally made in the thymus gland. Five of the patients taking the drug experienced a complete remission, and 11 showed a partial remission, for a major response rate of 36 percent.

"And all this occurred with very few side effects, which were limited mostly to mild headaches," said the study¹s principal investigator, Parkash Gill, M.D., professor of medicine and pathology at the Keck School of Medicine of the University of Southern California.

IM862 not only works, but it works quickly: The median amount of time it took for patients in the Phase I/II trials to respond was six to eight weeks. "It can take as much as 20-some weeks to see a complete response," said Gill, "but that¹s still fairly rapid."

And the drug¹s response lasts, as well. For 21 of the patients, the stabilization or regression of their disease has lasted between 7 and 72 weeks or more (at the time the data was compiled) -- even after they stopped taking the drug. "We have a number of patients who after stopping therapy have still not relapsed," Gill said.

The trial was conducted at the USC/Norris Comprehensive Cancer Center and Massachusetts General Hospital. Gill first unveiled his findings at the 35th annual meeting of the American Society of Clinical Oncology last May.

IM862, a peptide, is in development at Cytran Inc., of Kirkland, Wash. Its anti-angiogenic effect appears to be the result of a reduction in the production of a hormone called vascular endothelial growth factor (VEGF), said Gill. VEGF is the hormone responsible for new blood-vessel growth in the body. IM862 also appears to have immune system effects, enhancing the production of chemicals like interleukin-12 and thereby stimulating the body¹s so-called natural killer (NK) cells.

These two actions are closely intertwined. "NK cells produce factors that are toxic to endothelial cells," Gill explained, which means they can slow the growth of blood vessels as well as attack the tumor itself.

Recent laboratory analyses have shown that animals with pancreatic tumors who are treated with IM862 not only have a reduced rate of tumor growth, but have lower levels of VEGF as well. "This confirms quite nicely that at least one of the ways the drug is working is by anti-angiogenesis," Gill said.

Phase III trials of IM862 are now underway at the USC/Norris. In addition, IM862 is currently being tested as a treatment for ovarian cancer, colorectal cancer and melanoma. Gill and his colleagues are planning to begin a trial for prostate cancer, as well.

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EDITORS: See Anil Tulpule, David T. Scadden, Byron M. Espina, Suzanne Cabriales, Walter Howard, Kathleen Shea, Parkash Gill, "Results of a Randomized Study of IM862 Nasal Solution in the Treatment of AIDS-related Kaposi¹s Sarcoma," Journal of Clinical Oncology, Vol. 18, No. 4, [February] 2000.