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.
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.
Gardembas
Martine
M
Department of Oncology-Hematology and Cell Therapy, CHU La Milétrie, Rue de la Milètrie, 86021 Poitiers Cedex, France.
Rousselot
Philippe
P
Tulliez
Michel
M
Vigier
Magda
M
Buzyn
Agnes
A
Rigal-Huguet
Francoise
F
Legros
Laurence
L
Michallet
Mauricette
M
Berthou
Christian
C
Cheron
Nathalie
N
Maloisel
Frederic
F
Mahon
Francois-Xavier
FX
Facon
Thierry
T
Berthaud
Patrice
P
Guilhot
Joelle
J
Guilhot
Francois
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000097:blood; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000097:blood; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D012449:Safety; D013921:Thrombocytopenia / Q000139:chemically induced
D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl