The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Intermittent Target Inhibition With Dasatinib 100 mg Once Daily Preserves Efficacy and Improves Tolerability in Imatinib-Resistant and -Intolerant Chronic-Phase Chronic Myeloid Leukemia
Abstract
Purpose: Dasatinib is a BCR-ABL inhibitor, 325-fold more potent than imatinib against unmutated BCR-ABL in vitro. Phase II studies have demonstrated efficacy and safety with dasatinib 70 mg twice daily in chronic-phase (CP) chronic myelogenous leukemia (CML) after imatinib treatment failure. In phase I, responses occurred with once-daily administration despite only intermittent BCR-ABL inhibition. Once-daily treatment resulted in less toxicity, suggesting that toxicity results from continuous inhibition of unintended targets. Here, a dose- and schedule-optimization study is reported. Patients and Methods: In this open-label phase III trial, 670 patients with imatinib-resistant or -intolerant CP-CML were randomly assigned 1:1:1:1 between four dasatinib treatment groups: 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. Results: With minimum follow-up of 6 months (median treatment duration, 8 months; range, < 1 to 15 months), marked and comparable hematologic (complete, 86% to 92%) and cytogenetic (major, 54% to 59%; complete, 41% to 45%) response rates were observed across the four groups. Time to and duration of cytogenetic response were similar, as was progression-free survival (8% to 11% of patients experienced disease progression or died). Compared with the approved 70-mg twice-daily regimen, dasatinib 100 mg once daily resulted in significantly lower rates of pleural effusion (all grades, 7% v 16%; P = .024) and grade 3 to 4 thrombocytopenia (22% v 37%; P = .004), and fewer patients required dose interruption (51% v 68%), reduction (30% v 55%), or discontinuation (16% v 23%). Conclusion: Dasatinib 100 mg once daily retains the efficacy of 70 mg twice daily with less toxicity. Intermittent target inhibition with tyrosine kinase inhibitors may preserve efficacy and reduce adverse events.
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Self-citationDasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias
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Self-citationO'Hare, T., Walters, D. K., Stoffregen, E. P., Jia, T., Manley, P. W., Mestan, J., Cowan-Jacob, S. W., Lee, F. Y., Heinrich, M. C., Deininger, M. W. N., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0259 · Cited by 1,036
Self-citationRanson, M., Hammond, L. A., Ferry, D., Kris, M., Tullo, A., Murray, P. I., Miller, V., Averbuch, S., Ochs, J., Morris, C., et al. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.10.112 · Cited by 763
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Self-citationStrumberg, D., Clark, J. W., Awada, A., Moore, M. J., Richly, H., Hendlisz, A., Hirte, H. W., Eder, J. P., Lenz, H.-J., & Schwartz, B. (2007) · The Oncologist · doi:10.1634/theoncologist.12-4-426 · Cited by 419
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Self-citationKantarjian, H., Pasquini, R., Hamerschlak, N., Rousselot, P., Holowiecki, J., Jootar, S., Robak, T., Khoroshko, N., Masszi, T., Skotnicki, A., et al. (2007) · Blood · doi:10.1182/blood-2006-11-056028 · Cited by 377
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Baccarani, M., Cortes, J., Pane, F., Niederwieser, D., Saglio, G., Apperley, J., Cervantes, F., Deininger, M., Gratwohl, A., Guilhot, F., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.25.0779 · Cited by 1,291
Self-citationTranslation of the Philadelphia chromosome into therapy for CML
Druker, B. J. (2008) · Blood · doi:10.1182/blood-2008-07-077958 · Cited by 668
Cortes, J. E., Kim, D.-W., Pinilla-Ibarz, J., le Coutre, P. D., Paquette, R., Chuah, C., Nicolini, F. E., Apperley, J. F., Khoury, H. J., Talpaz, M., et al. (2018) · Blood · doi:10.1182/blood-2016-09-739086 · Cited by 592
Self-citationSteegmann, J. L., Baccarani, M., Breccia, M., Casado, L. F., García-Gutiérrez, V, Hochhaus, A., Kim, D.-W., Kim, T. D., Khoury, H. J., Le Coutre, P., et al. (2016) · Leukemia · doi:10.1038/leu.2016.104 · Cited by 482
Self-citationCortes, J. E., Kim, D.-W., Kantarjian, H. M., Brümmendorf, T. H., Dyagil, I., Griskevicius, L., Malhotra, H., Powell, C., Gogat, K., Countouriotis, A. M., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.38.7522 · Cited by 466
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Metadata
- Authors
- Shah, N. P., Kantarjian, H. M., Kim, D.-W., Réa, D., Dorlhiac-Llacer, P. E., Milone, J. H., Vela-Ojeda, J., Silver, R. T., Khoury, H. J., Charbonnier, A., Khoroshko, N., Paquette, R. L., Deininger, M., Collins, R. H., Otero, I., Hughes, T., Bleickardt, E., Strauss, L., Francis, S., & Hochhaus, A.
- Venue
- Journal of Clinical Oncology
- Published
- 2008-07-01
- Volume
- 26
- Issue
- 19
- Pages
- 3204-3212
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2116153687
- Cited by
- 489
- References
- 21
- FWCI
- 39.69
- Type
- journal article
- Language
- en
- Open access
- closed
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- Shah, N. P., Kantarjian, H. M., Kim, D.-W., Réa, D., Dorlhiac-Llacer, P. E., Milone, J. H., Vela-Ojeda, J., Silver, R. T., Khoury, H. J., Charbonnier, A., Khoroshko, N., Paquette, R. L., Deininger, M., Collins, R. H., Otero, I., Hughes, T., Bleickardt, E., Strauss, L., Francis, S., & Hochhaus, A. (2008). Intermittent Target Inhibition With Dasatinib 100 mg Once Daily Preserves Efficacy and Improves Tolerability in Imatinib-Resistant and -Intolerant Chronic-Phase Chronic Myeloid Leukemia. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2007.14.9260
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