SAN FRANCISCOResults of a phase II, open-label, multicenter
study show that the investigational agent STI571 holds promise for many
patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous
leukemia (CML) whose disease has proved resistant to interferon therapy.
After 6 months of STI571 therapy, 56% of patients experienced a
major cytogenetic response, Hagop Kantarjian, MD, said at the 42nd
Annual Meeting of the American Society of Hematology (ASH). The study was
sponsored by Novartis Oncology, which has named the new agent Glivec.
A total of 532 patients were enrolled in the study from 28
centers in the United States, France, Germany, Italy and the United Kingdom,
said Dr. Kantarjian, professor of medicine, Department of Hematology, M.D.
Anderson Cancer Center. STI571 was administered orally at a dose of 400 mg
Interferon failure was defined as a lack of complete
hematologic response despite 3 months of an interferon-containing regimen, or
as a lack of a cytogenetic response despite 1 year of an interferon-containing
regimen. Patients who had suffered a hematologic or cytogenetic relapse were
also included, as were patients with documented grade 3 interferon intolerance.
Among 388 patients treated with STI571 for 3 months, Dr.
Kantarjian said, more than 90% achieved a complete hematologic response (ie,
normalization of white blood cell counts), most within 4 to 6 weeks. Of these
patients, 37% also achieved an overall major cytogenetic response: 13% had a
complete cytogenetic response (0% Ph+ cells), and 23% had a partial response
(less than 35% Ph+ cells).
He also reported preliminary data on 290 patients who have
completed 6 months of STI571 therapy. Among these patients, 56% have had a
major cytogenetic response, with a complete cytogenetic response rate of 28%.
Among patients with less aggressive disease (less than 100% Ph+
cells), 78% had a major cytogenetic response. Patients who began STI571
treatment earlier in their disease (within a year of diagnosis) had a major
cytogenetic response rate of 62%.
"There was a concern that these cytogenetic responses
might not be durable," Dr. Kantarjian said. "But, in fact, that has
not been the case. There have been no patients with a cytogenetic response who
have evolved into blast crisis."
Dr. Kantarjian also noted that older patients responded as well
as the younger patients. (The median age in the study was 56 years).
"Given the toxicity of interferon in the older age groups, STI571 should
become the treatment of choice in these older patients," he said.
The most frequent adverse events in the study were nausea,
muscle cramps, headache, vomiting, fatigue, and diarrhea. Grade 3-4 toxicities,
including myelosuppression, were unusual, Dr. Kantarjian said, and occurred in
only about 3% of patients.
"These results are better than anything we’ve ever had
in patients with CML who had failure of interferon therapy," Dr.
Kantarjian said. "The official conclusion is that the data are very
encouraging and that the side effects are acceptable. But I would also like to
express my personal opinion that this is the most important drug we have ever
discovered for CML. Especially with patients treated early in their disease
with STI571, we are going to have results beyond any previous expectations. I
believe it should become front-line therapy."