Experimental Compound Targets Molecular Cause of Disease.
Patients with chronic myelogenous leukemia are finding new hope in an experimental pill developed by Oregon Health Sciences University researcher Brian Druker, M.D., in collaboration with scientists at Novartis Pharmaceuticals. Early clinical trials are producing dramatic results with minimal side effects.
Unlike chemotherapy, which kills both normal and abnormal cells in an attempt to eradicate the cancer, the compound STI-571 targets an enzyme found only in the leukemia cells. The result is a halt to the progression of the disease.
Druker will present Phase I clinical trial results at the American Society of Hematology conference in New Orleans on Dec. 5. The trial, conducted at OHSU in conjunction with Moshe Talpaz, M.D., at the M.D. Anderson Cancer Center in Houston and Charles Sawyers, M.D., the Jonsson Cancer Center at UCLA, involved CML patients who had failed to respond to standard treatment for their leukemia. Once an STI-571 dosage of 300 mg or greater was established, 31 of 31 patients in the study had a complete normalization of their blood counts, signaling a remission of the disease. Even more remarkable, in some cases the molecular cause of the disease seemed to disappear.
"I congratulate these investigators on pushing forward the field of rationally targeted cancer therapy," said Richard Klausner, M.D., director of the National Cancer Institute. "While too soon to evaluate the ultimate value of this agent for the standard clinical approach to CML, their early data are very encouraging."
"The early evidence of effectiveness of agent STI-571 heralds a new approach to leukemia therapy and perhaps that of other cancers as well, that is, the specific inactivation of the cancer-causing protein in malignant cells," said Marshall Lichtman, M.D., executive vice president for research and medical affairs of the Leukemia Society of America. "These preliminary results should engender excitement for researchers and physicians battling leukemia and new hope for affected patients. The Leukemia Society of America, on behalf of its donors and the patients we serve, is very pleased to have played an integral role in supporting this landmark research."
CML affects approximately 6,000 Americans a year and is characterized by an excessive proliferation of white blood cells. The disease is caused by a chromosomal defect that produces an abnormal enzyme called BCR-ABL, which is responsible for the overabundance of white blood cells. STI-571 was engineered to inhibit the activity of BCR-ABL.
"The potential significance of this type of research extends beyond leukemia," said Druker, whose research is supported in part by the Leukemia Society and the National Cancer Institute. "One of the major goals of cancer research has been to identify differences between cancer cells and normal cells so that these differences can be targeted with more effective and less toxic treatments. That's exactly what we've seen happen in these patients."
A Phase II trial, which will introduce the compound to a broader group of patients, is scheduled to begin in early 2000.