Browsing by Subject "Cytarabine"

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    ItemOpen Access
    Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: POG 9406: a report from the Children's Oncology Group.
    (Journal of pediatric hematology/oncology, 2014-07) Tower, Richard L; Jones, Tamekia L; Camitta, Bruce M; Asselin, Barbara L; Bell, Beverly A; Chauvenet, Allen; Devidas, Meenakshi; Halperin, Edward C; Pullen, Jeanette; Shuster, Jonathan J; Winick, Naomi; Kurtzberg, Joanne

    Purpose

    To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL).

    Patients and methods

    From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy.

    Results

    Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4%; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4% (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3%) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase.

    Conclusions

    Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy.
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    Phase 1/2 trial of GCLAM with dose-escalated mitoxantrone for newly diagnosed AML or other high-grade myeloid neoplasms.
    (Leukemia, 2018-11) Halpern, Anna B; Othus, Megan; Huebner, Emily M; Scott, Bart L; Becker, Pamela S; Percival, Mary-Elizabeth M; Hendrie, Paul C; Gardner, Kelda M; Chen, Tara L; Buckley, Sarah A; Orlowski, Kaysey F; Anwar, Asma; Appelbaum, Frederick R; Erba, Harry P; Estey, Elihu H; Walter, Roland B
    Outcomes with "7 + 3" are often unsatisfactory in acute myeloid leukemia (AML). Trials demonstrating improved outcomes with high-dose cytarabine, addition of cladribine, or escalated anthracycline doses prompted a phase 1/2 study (NCT02044796) of G-CSF, cladribine, high-dose cytarabine, and dose-escalated mitoxantrone (GCLAM) in adults with newly-diagnosed AML or other high-grade myeloid neoplasms. One hundred and twenty-one patients, median age 60 (range 21-81) years, were enrolled. In phase 1, cohorts of 6-12 patients were assigned to 12-18 mg/m2/day of mitoxantrone as part of GCLAM. Because all dose levels were well-tolerated, mitoxantrone at 18 mg/m2 was declared the recommended phase 2 dose (RP2D). 74/94 (79%) patients treated at the RP2D achieved a complete remission (CR; 67/74 without measureable residual disease [MRD]) for an overall MRDneg CR rate of 71% (primary phase 2 endpoint). Seven patients achieved a CR with incomplete blood count recovery (CRi; 7%, 5 MRDneg) for a CR/CRi rate of 81/94 (86%). Four-week mortality was 2%. After adjustment, the MRDneg CR and CR/CRi rates compared favorably to 100 matched controls treated with 7 + 3 at our center and 245 matched patients treated with 7 + 3 on a cooperative group trial. Our data indicate GCLAM with mitoxantrone at 18 mg/m2/day is safe and induces high-quality remissions in adults with newly-diagnosed AML.
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    ItemOpen Access
    Relative survival following response to 7 + 3 versus azacytidine is similar in acute myeloid leukemia and high-risk myelodysplastic syndromes: an analysis of four SWOG studies.
    (Leukemia, 2019-02) Othus, Megan; Sekeres, Mikkael A; Nand, Sucha; Garcia-Manero, Guillermo; Appelbaum, Frederick R; Erba, Harry P; Estey, Eli
    Here we quantify and compare the absolute and relative overall survival (OS) benefits conveyed by complete remission (CR) in AML and high-risk MDS, and by CR with incomplete count recovery (CRi) in AML and by hematologic improvement (HI) in MDS, following treatment with 7 + 3 versus azacytidine. We compared patients receiving 7 + 3 in SWOG studies S0106 (n = 301) and S1203 (n = 261) enrolling adults ≤ 60 years, with patients receiving azacytidine therapies in S0703 (n = 133 AML patients ≥ 60) and S1117 (n = 277 MDS patients ≥ 18). Absolute survival benefit was evaluated with 1-year, 3-year, and median OS; relative benefit was evaluated with univariate and covariate-adjusted hazard ratios. CR conveyed a relative survival advantage in multivariable analysis, with a similar relative effect of CR across studies. CR also conferred an absolute survival benefit, but with a smaller magnitude of absolute benefit in the azacytidine trials. In AML, OS was similar for CRi and failure to achieve CR/CRi. In MDS, CR conferred a survival advantage versus HI and HI versus failure. The relative survival benefit of CR was similar regardless of initial therapy for AML or high-risk MDS. With both therapies, CR has a beneficial effect on survival compared with CRi or HI.