Results of a prospective phase 2 study combining imatinib mesylate and cytarabine for the treatment of Philadelphia-positive patients with chronic myelogenous leukemia in chronic phase

• Published in: Blood 2003-12, Vol.102 (13), p.4298-4305
• Main Authors: Gardembas, Martine, Rousselot, Philippe, Tulliez, Michel, Vigier, Magda, Buzyn, Agnès, Rigal-Huguet, Françoise, Legros, Laurence, Michallet, Mauricette, Berthou, Christian, Cheron, Nathalie, Maloisel, Frederic, Mahon, François-Xavier, Facon, Thierry, Berthaud, Patrice, Guilhot, Joëlle, Guilhot, François
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzamides; Biological and medical sciences; Biomarkers, Tumor - blood; Cytarabine - administration & dosage; Cytarabine - adverse effects; Drug Administration Schedule; Female; Fusion Proteins, bcr-abl - blood; Hematologic and hematopoietic diseases; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myeloid, Chronic-Phase - drug therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Neutropenia - chemically induced; Piperazines - administration & dosage; Piperazines - adverse effects; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Remission Induction; Safety; Thrombocytopenia - chemically induced
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-04-1010

In chronic myelogenous leukemia (CML) imatinib mesylate has been shown to selectively inhibit the tyrosine kinase domain of the oncogenic bcr-abl fusion protein. Using this agent alone high rates of cytogenetic responses were recorded. However, several mechanisms of resistance have been described. In vitro studies examining the effects of imatinib mesylate plus cytarabine have shown synergistic antiproliferative effects of this combination. Thus, the CML French Group decided to perform a phase 2 trial testing a combination of imatinib mesylate and low-dose cytarabine in 30 previously untreated patients in chronic phase. Treatment was administered on 28-day cycles. Patients were treated continuously with imatinib mesylate orally at a dose of 400 mg daily. Cytarabine was given on days 15 to 28 of each cycle at an initial dose of 20 mg/m2/d via subcutaneous injection. Adverse events were frequently observed with grade 3 or 4 hematologic toxicities and nonhematologic toxicities in 53% (n = 16) and 23% (n = 7) of patients, respectively. The cumulative incidence of complete cytogenetic response (CCR) at 12 months was 83% and at 6 months 100% of the patients achieved complete hematologic response (CHR). We concluded that the combination was safe and promising given the rates of response. (Blood. 2003;102:4298-4305)