STI571 Studies Help Validate Molecular Targeting in CML

News
Article
Oncology NEWS InternationalOncology NEWS International Vol 10 No 1
Volume 10
Issue 1

NEW YORK-The promise of molecularly targeted therapies has been validated in chronic myelogenous leukemia (CML), Brian J. Druker, MD, of Oregon Health Sciences University, Portland, said at the Chemotherapy Foundation Symposium XVIII. "This disease has provided an ideal opportunity to test the concept that drugs targeted against a tumor-specific abnormality will have therapeutic utility," he said.

NEW YORK—The promise of molecularly targeted therapies has been validated in chronic myelogenous leukemia (CML), Brian J. Druker, MD, of Oregon Health Sciences University, Portland, said at the Chemotherapy Foundation Symposium XVIII. "This disease has provided an ideal opportunity to test the concept that drugs targeted against a tumor-specific abnormality will have therapeutic utility," he said.

That molecular abnormality is the Bcr-Abl fusion protein, which results from a chromosome translocation and causes several kinds of leukemia. It is unique to tumor cells and is present in almost every CML patient.

Bcr-Abl kinase activity has been shown to be essential to CML pathogenesis. Thus, as predicted, the investigational tyrosine kinase inhibitor STI571 was a selective and effective therapy in this disease. [See article on page 2 for results in interferon-failure CML patients.]

"STI571 represents an example of successful drug development based on a specific molecular abnormality present in human malignancy," Dr. Druker said.

Preclinical testing showed that STI571 was selectively toxic to cells that express the constitutively active Bcr-Abl protein tyrosine kinase. It was highly bioavailable in an oral formulation. Antitumor activity was seen in mice that had been injected with cells expressing Bcr-Abl and treated with STI571. No safety concerns emerged in animal testing.

In a phase I trial of CML patients who had failed previous treatment, all 31 patients with chronic phase disease achieved hematologic remissions after reaching therapeutic dosing levels. Cytogenetic responses were seen in a "growing fraction" of patients after prolonged therapy of 5 months or more, he said.

Newsletter

Stay up to date on recent advances in the multidisciplinary approach to cancer.

Recent Videos
Increasing the use of patient-reported outcomes may ensure that practitioners can fully ascertain the impact of treatment for rare lymphomas.
Retrospective and real-world registry studies may be necessary to guide clinical decision-making for rarer lymphomas with insufficient prospective data.
Ongoing studies seek to evaluate immunotherapy in earlier lines of therapy for patients with early-stage Hodgkin lymphoma.
A paucity of prospective, well-vetted data to guide therapy in patients with rare lymphomas may result in a reliance on expert consensus guidelines.
Both clinicians and patients should have as much information as possible to participate in shared decision-making for CLL care, says Jacob D. Soumerai, MD.
Sequencing different treatments in the first 3 lines of therapy represents a challenge in chronic lymphocytic leukemia, according to Deborah Stephens, DO.
Related Content