Dose modification of imatinib by monitoring the level of BCR-ABL transcript in chronic myelogenous leukemia.

Abstract

Chronic myelogenous leukemia (CML) is a hematological malignancy that is characterized by the chromosome anomaly, t(9;22)(q34;q11). By this chromosomal translocation, a novel activated tyrosine kinase, BCR-ABL chimeric protein, is generated, and the protein is causative of the disease. Recently, Imatinib mesylate targeting to a BCR-ABL chimeric protein has been developed, and shown to achieve complete remission at a high rate. Patients are currently required to receive a fixed dose, 400 mg daily; however, it is possible that some of patients can maintain their remission with reduced doses of imatinib. In this study, we determined levels of BCR-ABL transcript in CML patients by real-time quantitative polymerase chain reaction analysis, and explored the possibility of individualization of therapeutic doses of imatinib. Thirty-five CML patients, including 17 newly diagnosed patients, 16 patients pre-treated with interferon-alpha, and 2 relapsed patients after allogeneic transplantation, were treated with imatinib. Complete cytogenetic response was achieved in 31 (89%) patients. Major molecular response (MMR) was achieved in 21 (60%). Complete molecular response (CMR) was achieved in 7 (20%). Imatinib was discontinued in 2 patients, one patient with MMR due to noncompliance and other patient sustaining CMR, but both patients relapsed 7 and 13 months later, respectively. The doses of imatinib were reduced in 7 patients due to its side effects, but 4 out of the 7 patients have sustained MMR, and 2 of them have sustained CMR for more than 23 months. These results indicate that some patients are able to maintain MMR with low-dose imatinib.

• Authors: Izumi Ishikawa, Chiaki Kato, Hideo Harigae, Tomohiro Sugawara, Yasuo Tomiya, Minami Yamada, Kenichi Ishizawa, Junichi Kameoka, Koichi Miyamura, Takeshi Sasaki
• Journal: The Tohoku journal of experimental medicine (Tohoku J Exp Med) Vol. 210 Issue 4 Pg. 355-63 (Dec 2006) ISSN: 0040-8727 [Print] Japan
• PMID: 17146202 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antineoplastic Agents
• Benzamides
• Biomarkers, Tumor
• Piperazines
• Pyrimidines
• Imatinib Mesylate
• Fusion Proteins, bcr-abl

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage)
• Benzamides
• Biomarkers, Tumor (analysis)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Fusion Proteins, bcr-abl (blood)
• Humans
• Imatinib Mesylate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (blood, drug therapy, genetics)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Patient Care Planning
• Piperazines (administration & dosage)
• Polymerase Chain Reaction
• Pyrimidines (administration & dosage)
• Remission Induction
• Treatment Outcome