Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study

Larson, Richard A.; Druker, Brian J.; Guilhot, Joëlle; O’Brien, Stephen G.; Rivière, Gilles; Krahnke, Tillmann; Gathmann, Insa; Wang, Yanfeng

doi:10.1182/blood-2007-10-116475

Cited by 557 publications

(587 citation statements)

References 29 publications

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“…In a subanalysis of the IRIS trial ( n = 351), significantly reduced incidences of major molecular and complete cytogenetic response and a trend towards reduced event‐free survival were observed in the lowest C min quartile 19. Another study in Japanese patients found ( n = 254) found a significant correlation between C min ≥1,002 ng/ml and higher probability of achieving a major molecular response 20…”

Section: Practical Recommendations For Tdm Of Kis In Oncologymentioning

confidence: 99%

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Verheijen

Schellens

et al. 2017

Clin Pharma and Therapeutics

218

260

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Despite the fact that pharmacokinetic exposure of kinase inhibitors (KIs) is highly variable and clear relationships exist between exposure and treatment outcomes, fixed dosing is still standard practice. This review aims to summarize the available clinical pharmacokinetic and pharmacodynamic data into practical guidelines for individualized dosing of KIs through therapeutic drug monitoring (TDM). Additionally, we provide an overview of prospective TDM trials and discuss the future steps needed for further implementation of TDM of KIs.

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Section: Practical Recommendations For Tdm Of Kis In Oncologymentioning

confidence: 99%

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Verheijen

Schellens

et al. 2017

Clin Pharma and Therapeutics

218

260

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“…e l s e v i e r . c o m / l o c a t e / c l i n b i o c h e m to treatment, which, in turn, correlates with clinical outcome [3]. Picard et al determined that the ideal trough IM plasma concentration should be at least 1000 ng/mL [4].…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

The clinical relevance of imatinib plasma trough concentrations in chronic myeloid leukemia. A Belgian study

Obbergh

Knoops

Devos

et al. 2017

Clinical Biochemistry

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This retrospective multicenter study in patients with chronic myeloid leukemia in chronic phase was undertaken to confirm the clinical relevance of imatinib plasma concentrations monitoring in daily practice. Forty-one patients, with 47 imatinib plasma measurements, were analyzed during treatment with imatinib given at a fixed 400 mg daily dose. A significant inverse relationship of imatinib concentration with the patients' weight was observed (Pearson's test: p = 0.02, R 2 = 0.1). More interestingly, patients with poor response (switched to another tyrosine kinase inhibitor because of imatinib failure, or because of disease progression after an initial response) displayed a significantly lower mean imatinib concentration as compared to patients maintained on imatinib (822 ng/mL vs 1099 ng/mL; Student's t-test, p = 0.04). Failure or disease progression occurred more often in patients in the lowest quartile of imatinib concentrations compared to patients in the highest quartile (p = 0.02, logrank test). No correlation could be established with other biological or clinical parameter, including complete cytogenic response and major molecular response. In conclusion: in patients treated with imatinib at a fixed daily dose of 400 mg, imatinib plasma concentrations decreased with increasing body weight and were lower in patients switched to another tyrosine kinase inhibitor due to imatinib failure. Systematic determination of imatinib plasma trough levels should be encouraged in such patients.

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“…Imatinib trough blood level concentrations at 4 weeks into therapy have been associated with outcome. 34 Imatinib blood level testing also may be useful when a patient does not achieve or has lost an optimal response, exhibits signs of potential drug-drug interactions, or is experiencing unusually severe side effects. However, the results of individual imatinib blood level tests should be considered with caution, because they may not be a true reflection of long-term imatinib blood levels and, thus, may not necessarily have an impact on the course of therapy.…”

Section: Imatinib Nilotinib Dasatinibmentioning

confidence: 99%

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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Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study

Cited by 557 publications

References 29 publications

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

The clinical relevance of imatinib plasma trough concentrations in chronic myeloid leukemia. A Belgian study

Optimizing therapy for patients with chronic myelogenous leukemia in chronic phase

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