A second-generation cancer drug offers one last shot at life for leukemia patients who have not been helped by the "miracle" drug Gleevec, doctors reported earlier this month.
Tests on mice show the experimental drug overcomes virtually all of the genetic mutations that cause some cancers to resist treatment with Gleevec, the researchers report.
Gleevec, made by Swiss drug company Novartis AG and sold in Europe under the name Glivec, was the first "targeted" cancer drug.
The findings, published in the latest issue of the journal Science this month, add to evidence that precisely targeted cancer drugs can be designed quickly and rushed into testing for the most desperate cancer patients.
Unpublished findings, which the researchers may not discuss, suggest the new drug is working safely and in some cases dramatically in some chronic myeloid leukemia (CML) patients who had run out of options.
"We hope this represents another viable treatment option for patients with this disease," said Dr Neil Shah of the University of California, Los Angeles, who worked on the study. "There may now be hope beyond Gleevec should they suffer a relapse."
Taken as a pill, the drug produced remarkable results in patients with advanced CML, an immune-system cancer that kills about half the 4,000 or so people affected by the disease in the United States each year.
But about 15 percent of patients are not helped by Gleevec. Researchers discovered a series of genetic mutations in their tumours that helped the cancer cells evade its effects.
Gleevec, known chemically as imatinib, works by attaching to and blocking an enzyme called BCR-ABL that helps leukemia cells grow. Mutations in this enzyme change its shape enough so that Gleevec cannot attach itself.
"We realized if we want to develop drugs that inhibit the mutants, they need to be a little sloppier, less demanding in their binding rules," said Dr Charles Sawyers, a Howard Hughes Medical Institute researcher at UCLA.
Members of a closely related class of drugs called SRC inhibitors also sometimes attach to and block ABL, he discovered. "Bristol Myers Squibb had a SRC inhibitor programme and they called me," added Sawyer, who worked on the development of Gleevec and led the study.
One drug, BMS-354825 being developed by Bristol-Myers Squibb, looked like it would work perfectly against the mutated versions of CML cells.
Shah said it took only three years to develop the new drug - light-speed in terms of cancer therapy. And the science has advanced to where a curious doctor can tell a patient with CML why he is or is not being helped by a drug.
"I can tell them why they are resistant. I can tell them whether they are likely to respond to this new agent," Shah said. "We hope that this is the first of many diseases to be treated this way."
Sawyers and colleagues reported on mice and tests in lab dishes of human cancer cells. They said the new drug was active against 14 out of 15 different Gleevec-resistant tumours.
The drug is in Phase I safety trials in CML patients in Los Angeles and Houston and at least one patient says he is seeing clear results.
Shah said the Phase I trial is still in the dose-escalating phase, meaning they are raising doses of the new drug to the highest levels they can without seeing serious side-effects.
(China Daily July 19, 2004)
