Imatinib and pegylated human recombinant interferon-alpha2b in early chronic-phase chronic myeloid leukemia.
Since interferon-alpha and imatinib (IM; STI571, Glivec, Gleevec) are effective for the treatment of chronic myeloid leukemia (CML), and their mechanisms of action are different, we designed an exploratory study investigating the effects of a standard IM dose (400 mg/d) and a variable pegylated interferon-alpha (PegIFN) dose (50 microg/wk, 100 microg/wk, and 150 microg/wk). The criteria for dose adjustment were designed so as to ensure the delivery of the IM dose and to protect life quality. There were 76 patients with previously untreated Philadelphia (Ph)-positive CML enrolled in the study. There were 3 patients who discontinued IM and 45 patients who discontinued PegIFN. The severity of adverse events increased with increasing PegIFN dose. The IM dose could be administered to the patients who were assigned to receive 50 microg/wk or 100 microg/wk PegIFN but not to those who were assigned to receive 150 microg/wk. The median administered dose of PegIFN ranged between 32 microg/wk and 36 microg/wk. The cytogenetic response was 70% complete (Ph-neg 100%) and 83% major (Ph-neg > 65%). The BCR/ABL transcript was reduced by at least 3 logs in 68% of complete cytogenetic responders. These data of toxicity, compliance, and efficacy may assist in the design and preparation of prospective studies.
Institute of Hematology and Medical Oncology L. and A. Seràgnoli, University of Bologna, Via Massarenti, 9-40138 Bologna, Italy. baccarani@med.unibo.it
Michele
M
Baccarani
Giovanni
G
Martinelli
Gianantonio
G
Rosti
Elena
E
Trabacchi
Nicoletta
N
Testoni
Simona
S
Bassi
Marilina
M
Amabile
Simona
S
Soverini
Fausto
F
Castagnetti
Daniela
D
Cilloni
Barbara
B
Izzo
Antonio
A
de Vivo
Emanuela
E
Messa
Francesca
F
Bonifazi
Angela
A
Poerio
Simona
S
Luatti
Emilia
E
Giugliano
Daniele
D
Alberti
Gianluca
G
Fincato
Domenico
D
Russo
Fabrizio
F
Pane
Giuseppe
G
Saglio
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D001549:Benzamides; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000633:toxicity; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000633:toxicity; D011743:Pyrimidines / Q000008:administration & dosage* / Q000633:toxicity; D011994:Recombinant Proteins
D001549:Benzamides; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D011994:Recombinant Proteins; D000068877:Imatinib Mesylate