The Effect of Dose Increase of Imatinib Mesylate in Patients with Chronic or Accelerated Phase Chronic Myelogenous Leukemia with Inadequate Hematologic or Cytogenetic Response to Initial Treatment

• Published in: Clinical cancer research 2003-06, Vol.9 (6), p.2092-2097
• Main Authors: ZONDER, Jeffrey A, PEMBERTON, Pamela, BRANDT, Helen, MOHAMED, Anwar N, SCHIFFER, Charles A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Benzamides; Biological and medical sciences; Chemotherapy; Female; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - blood; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myeloid, Accelerated Phase - blood; Leukemia, Myeloid, Accelerated Phase - drug therapy; Leukemia, Myeloid, Accelerated Phase - genetics; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Philadelphia Chromosome; Piperazines - administration & dosage; Piperazines - adverse effects; Pyrimidines - administration & dosage; Pyrimidines - adverse effects
• ISSN: 1078-0432; 1557-3265

Purpose: Imatinib mesylate is a tyrosine kinase inhibitor with high affinity for the BCR-ABL fusion protein expressed by the hematopoietic cells in chronic myelogenous leukemia (CML). Some patients with chronic-phase or accelerated-phase CML either relapse after an initial response or are refractory to imatinib, prompting us to evaluate the efficacy of dose increase in such patients. Experimental Design: Twelve chronic-phase patients initially receiving 400 mg/day and 4 patients with accelerated phase initially receiving either 400 mg/day (two patients) or 600 mg/day (two patients) had their dose increased (14 to 800 mg/day and 2 to 600 mg/day) because of progressive disease (usually clonal evolution) or inadequate cytogenetic response after at least 1 year of therapy. Results: Six patients had major cytogenetic responses after dose increase (3 complete and 3 partial). Two others had minor cytogenetic responses. Two patients with clonal evolution transiently lost the additional clonal aberrations. Almost all of the responses occurred within 6 months, and were typically 3–6 months in duration. However, 3 patients have continuing major cytogenetic responses of >18 months duration. Dose increase was well tolerated, with thrombocytopenia, mild leukopenia, and exacerbation of prior edema being the most common adverse events. Conclusions: Although increasing the dose of imatinib can benefit a subgroup of patients with CML with either an inadequate cytogenetic response or disease progression, our results suggest the majority will not have a sustained meaningful response, and that other options, such as allogeneic stem cell transplant or investigational therapies, also need to be considered at the time of dose increase.