title: Impact of early dose intensity on cytogenetic and molecular responses in chronic- phase CML patients receiving 600 mg/day of imatinib as initial therapy.
abstract: We conducted a trial in 103 patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML) using imatinib 600 mg/day, with dose escalation to 800 mg/day for suboptimal response. The estimated cumulative incidences of complete cytogenetic response (CCR) by 12 and 24 months were 88% and 90%, and major molecular responses (MMRs) were 47% and 73%. In patients who maintained a daily average of 600 mg of imatinib for the first 6 months (n = 60), MMR rates by 12 and 24 months were 55% and 77% compared with 32% and 53% in patients averaging less than 600 mg (P = .037 and .016, respectively). Dose escalation was indicated for 17 patients before 12 months for failure to achieve, or maintain, major cytogenetic response at 6 months or CCR at 9 months but was only possible in 8 patients (47%). Dose escalation was indicated for 73 patients after 12 months because their BCR-ABL level remained more than 0.01% (international scale) and was possible in 45 of 73 (62%). Superior responses achieved in patients able to tolerate imatinib at 600 mg suggests that early dose intensity may be critical to optimize response in CP-CML. The trial was registered at www.ANZCTR.org.au as #ACTRN12607000614493.
authors.affiliation: Institute of Medical and Veterinary Science, Adelaide, Australia. timothy.hughes@imvs.sa.gov.au
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Hughes
authors.forename: Susan
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authors.forename: Deborah L
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authors.lastname: White
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authors.forename: John F
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authors.lastname: Rowlings
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authors.lastname: Hertzberg
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authors.lastname: Mills
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authors.lastname: Durrant
authors.forename: Henry
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authors.lastname: Januszewicz
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authors.forename: Andrew
authors.initials: A
authors.lastname: Grigg