Intermittent Target Inhibition With Dasatinib 100 mg Once Daily Preserves Efficacy and Improves Tolerability in Imatinib-Resistant and -Intolerant Chronic-Phase Chronic Myeloid Leukemia

Shah, Neil P.; Kantarjian, Hagop M.; Kim, Dong Wook; Réa, Delphine; Dorlhíac-Llacer, Pedro Enrique; Milone, Jorge; Vela‐Ojeda, Jorge; Silver, Richard T.; Khoury, H. Jean; Charbonnier, Aude; Хорошко, Н. Д.; Paquette, Ronald; Deininger, Michael W.; Collins, Robert H.; Otero, I. Rodríguez-M.; Hughes, Timothy P.; Bleickardt, Eric; Strauss, Lewis C.; Francis, Stephen; Hochhaus, Andreas

doi:10.1200/jco.2007.14.9260

Cited by 436 publications

(477 citation statements)

References 23 publications

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“…70 To minimize dasatinib-related toxicity while maintaining efficacy, a dose-optimization study was initiated. 74 In that phase 3 trial, 670 patients with imatinib-resistant or imatinib-intolerant CML-CP were randomized to receive 1 of 4 doses of dasatinib: 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. Patients who received dasatinib once daily (100 mg once daily) achieved an MCyR rate comparable to that achieved by patients who received dasatinib twice daily (70 mg twice daily).…”

Section: Dasatinibmentioning

confidence: 99%

“…It is noteworthy that the rates of grade 3/4 hematologic and nonhematologic toxicities, including pleural effusions, were decreased with 100 mg once-daily dasatinib dosing. 74 Currently, a once-daily dose of 100 mg is approved for patients with CML-CP based on these findings. Dasatinib at 70 mg twice daily and 140 mg once daily currently are dosing options for patients with CML-AP and CML-BC.…”

Section: Dasatinibmentioning

confidence: 99%

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Optimizing therapy for patients with chronic myelogenous leukemia in chronic phase

Kantarjian

Cortés

Rosée

et al. 2010

Cancer

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Identification of BCR‐ABL as the defining leukemogenic event in chronic myelogenous leukemia (CML) revolutionized the treatment of the disease. Imatinib, a potent BCR‐ABL inhibitor, is the standard of care for the first‐line treatment of patients with chronic‐phase CML because of its high long‐term response rates and favorable tolerability profile compared with previous standard therapies. However, resistance to imatinib develops in 2% to 4% of patients annually. For patients with acquired cytogenetic resistance to standard‐dose imatinib (400 mg daily), imatinib dose escalation (600‐800 mg daily) is an excellent first option for managing patients and achieving cytogenetic responses. However, for patients with primary resistance to imatinib, hematologic disease recurrence, or emergent BCR‐ABL kinase domain mutations, imatinib dose escalation may not be sufficient to control the disease. For these patients, the potent second‐generation tyrosine kinase inhibitors dasatinib and nilotinib are available. Both agents provide effective therapeutic options for patients with imatinib resistance or intolerance. For the current overview, the authors reviewed the data supporting the use of both dasatinib and nilotinib in imatinib‐resistant or imatinib‐intolerant patients, and they have highlighted the future of CML therapy. Overall, the article is intended to offer physicians a comprehensive review of the current literature and to provide data supporting various treatment options for patients with CML throughout the course of imatinib therapy and beyond. Cancer 2010. © 2010 American Cancer Society.

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Section: Dasatinibmentioning

confidence: 99%

Section: Dasatinibmentioning

confidence: 99%

Optimizing therapy for patients with chronic myelogenous leukemia in chronic phase

Kantarjian

Cortés

Rosée

et al. 2010

Cancer

Self Cite

View full text Add to dashboard Cite

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“…Second-line therapy with dasatinib is further supported by an open-label phase III trial of patients with imatinib-resistant or -intolerant chronic phase CML, with long-term follow-up to 6 years [55,56]. The trial showed that dasatinib 100 mg once daily (OD) had comparable efficacy to the licensed 70 mg twice daily (BID) dose, but with a more favorable tolerability profile, including significantly lower rates of grade 3/4 thrombocytopenia and all-grade pleural effusion [53].…”

Section: Dasatinibmentioning

confidence: 99%

Chronic myeloid leukemia: Second‐line drugs of choice

Gambacorti‐Passerini

Cordani

2015

American J Hematol

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The efficacy of second-line treatment for chronic myeloid leukemia (CML) plays an important role in allowing CML patients to enjoy a normal life expectancy. Four tyrosine kinase inhibitors (TKIs) are presently available: bosutinib, dasatinib, nilotinib, ponatinib. Each one has different safety and activity profiles, which are reviewed here. No controlled studies are available to guide treatment decision, which must be based on the characterization of leukemic cells, especially in cases of resistance to TKI, coupled with the safety profile of each TKI. Patient comorbidities also play an important role in the treatment decision, which can achieve a new durable response in over 50% of treated patients.

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“…ALL) at a dosage of 70 mg twice daily. Results from a recent phase III dose-optimization study recently prompted a change in the recommended daily dose for patients with CP CML [70].…”

Section: F359mentioning

confidence: 99%

Extending the duration of response in chronic myelogenous leukemia: targeted therapy with sequential tyrosine kinase inhibitors

Martin

DiPersio

2009

Oncol Rev

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Tyrosine kinase inhibitors (TKIs) are the mainstay for treatment of chronic myelogenous leukemia (CML). Imatinib was the first TKI approved for use in CML, but resistance to this therapy has emerged as a significant issue, and second-line options are often necessary. Increased-dose imatinib may elicit responses in some patients, but clinical evidence suggests only a minority experience sustained benefit. The second-generation TKIs, dasatinib and nilotinib, have demonstrated efficacy in patients resistant or intolerant to imatinib. Changes in therapy, with the aim of inducing durable response, should occur promptly after imatinib failure is identified as all agents are more effective in chronic phase disease than in later stages. Selection of second-line agents should be driven by efficacy and safety: dasatinib may be more effective in patients with P-loop or F359C mutations; nilotinib may be more effective in those with F317L mutations.

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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: 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.

Cited by 436 publications

References 23 publications

Optimizing therapy for patients with chronic myelogenous leukemia in chronic phase

Optimizing therapy for patients with chronic myelogenous leukemia in chronic phase

Chronic myeloid leukemia: Second‐line drugs of choice

Extending the duration of response in chronic myelogenous leukemia: targeted therapy with sequential tyrosine kinase inhibitors

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