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Erschienen in: International Journal of Hematology 5/2009

01.06.2009 | Original Article

Relationship between an effective dose of imatinib, body surface area, and trough drug levels in patients with chronic myeloid leukemia

verfasst von: Tatsuya Kawaguchi, Akinobu Hamada, Chie Hirayama, Reiko Nakashima, Takeru Nambu, Yuji Yamakawa, Hiroshi Watanabe, Kentaro Horikawa, Hiroaki Mitsuya, Hideyuki Saito

Erschienen in: International Journal of Hematology | Ausgabe 5/2009

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Abstract

The standard dose of imatinib for the treatment of chronic-phase chronic myeloid leukemia (CML) is 400 mg/day. Some patients receive reduced doses of imatinib because of serious adverse effects. Recently, the effective plasma threshold for trough imatinib levels was demonstrated to be 1,002 ng/mL. In this study, we evaluated the association of an imatinib dose with trough plasma concentrations and clinical outcomes in 31 patients with chronic-phase CML who were treated at Kumamoto University Hospital. Twenty-seven patients were optimally treated with various doses of imatinib. The mean (±SD) trough plasma concentrations of imatinib were 1.40 ± 0.57 μg/mL in 13 patients receiving 400 mg/day and 1.15 ± 0.44 μg/mL in 9 patients receiving 300 mg/day as an effective dose. Mean trough levels of the two groups were not significantly different and exceeded the effective plasma threshold. Body surface area (BSA) was significantly smaller in patients receiving the reduced dose compared with those receiving the standard dose (p = 0.001). The effective imatinib dose was associated with age and gender as well as BSA. A reduced dose of 300 mg/day of imatinib may be sufficient for the treatment of CML patients with smaller body size, particularly when intolerability arises.
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Literatur
1.
2.
Zurück zum Zitat O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994–1004. doi:10.1056/NEJMoa022457.PubMedCrossRef O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994–1004. doi:10.​1056/​NEJMoa022457.PubMedCrossRef
3.
Zurück zum Zitat Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–17. doi:10.1056/NEJMoa062867.PubMedCrossRef Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–17. doi:10.​1056/​NEJMoa062867.PubMedCrossRef
4.
Zurück zum Zitat Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347:472–80. doi:10.1056/NEJMoa020461.PubMedCrossRef Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347:472–80. doi:10.​1056/​NEJMoa020461.PubMedCrossRef
5.
Zurück zum Zitat Peng B, Hayes M, Resta D, Racine-Poon A, Druker BJ, Talpaz M, et al. Pharmacokinetics and pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patients. J Clin Oncol. 2004;22:935–42. doi:10.1200/JCO.2004.03.050.PubMedCrossRef Peng B, Hayes M, Resta D, Racine-Poon A, Druker BJ, Talpaz M, et al. Pharmacokinetics and pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patients. J Clin Oncol. 2004;22:935–42. doi:10.​1200/​JCO.​2004.​03.​050.PubMedCrossRef
7.
Zurück zum Zitat Picard S, Titier K, Etienne G, Teilhet E, Ducint D, Bernard MA, et al. Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood. 2007;109:3496–9. doi:10.1182/blood-2006-07-036012.PubMedCrossRef Picard S, Titier K, Etienne G, Teilhet E, Ducint D, Bernard MA, et al. Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood. 2007;109:3496–9. doi:10.​1182/​blood-2006-07-036012.PubMedCrossRef
8.
Zurück zum Zitat Larson RA, Druker BJ, Guilhot FA, O’Brien SG, Riviere GJ, Krahnke T, et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood. 2008;111:4022–8. doi:10.1182/blood-2007-10-116475.PubMedCrossRef Larson RA, Druker BJ, Guilhot FA, O’Brien SG, Riviere GJ, Krahnke T, et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood. 2008;111:4022–8. doi:10.​1182/​blood-2007-10-116475.PubMedCrossRef
10.
Zurück zum Zitat Park SJ, Choi IK, Seo HY, Sung HJ, Park KH, Kim SJ, et al. Reduced dose of imatinib for patients with chronic myeloid leukemia and low body surface area. Acta Haematol. 2007;118:219–21. doi:10.1159/000111777.PubMedCrossRef Park SJ, Choi IK, Seo HY, Sung HJ, Park KH, Kim SJ, et al. Reduced dose of imatinib for patients with chronic myeloid leukemia and low body surface area. Acta Haematol. 2007;118:219–21. doi:10.​1159/​000111777.PubMedCrossRef
11.
Zurück zum Zitat Kanda Y, Okamoto S, Tauchi T, Kizaki M, Inokuchi K, Yabe M, et al. Multicenter prospective trial evaluating the tolerability of imatinib for Japanese patients with chronic myelogenous leukemia in the chronic phase: dose body weight matter? Am J Hematol. 2008;83:835–9. doi:10.1002/ajh.21274.PubMedCrossRef Kanda Y, Okamoto S, Tauchi T, Kizaki M, Inokuchi K, Yabe M, et al. Multicenter prospective trial evaluating the tolerability of imatinib for Japanese patients with chronic myelogenous leukemia in the chronic phase: dose body weight matter? Am J Hematol. 2008;83:835–9. doi:10.​1002/​ajh.​21274.PubMedCrossRef
12.
Zurück zum Zitat Ohnishi K, Nishimura M, Takeuchi J, Fujisawa S, Nagai T, Miyamura K, et al. Lower dose of imatinib provides outcomes similar to the standard dose imatinib in Japanese patients with early chronic-phase CML: the interim analyses of JALSG CML202 Study. Blood. 2007;110:316a. Ohnishi K, Nishimura M, Takeuchi J, Fujisawa S, Nagai T, Miyamura K, et al. Lower dose of imatinib provides outcomes similar to the standard dose imatinib in Japanese patients with early chronic-phase CML: the interim analyses of JALSG CML202 Study. Blood. 2007;110:316a.
15.
Zurück zum Zitat Dulucq S, Bouchet S, Turcq B, Lippert E, Etienne G, Reiffers J, et al. Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood. 2008;112:2024–7. doi:10.1182/blood-2008-03-147744.PubMedCrossRef Dulucq S, Bouchet S, Turcq B, Lippert E, Etienne G, Reiffers J, et al. Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood. 2008;112:2024–7. doi:10.​1182/​blood-2008-03-147744.PubMedCrossRef
Metadaten
Titel
Relationship between an effective dose of imatinib, body surface area, and trough drug levels in patients with chronic myeloid leukemia
verfasst von
Tatsuya Kawaguchi
Akinobu Hamada
Chie Hirayama
Reiko Nakashima
Takeru Nambu
Yuji Yamakawa
Hiroshi Watanabe
Kentaro Horikawa
Hiroaki Mitsuya
Hideyuki Saito
Publikationsdatum
01.06.2009
Verlag
Springer Japan
Erschienen in
International Journal of Hematology / Ausgabe 5/2009
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-009-0315-4

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