Relationship between daily dose of imatinib per square meter and its plasma concentration in patients with chronic-phase chronic myeloid leukemia (CML)

Horikoshi, Akira; Takei, Kazuhiro; Sawada, Shigemasa

doi:10.1016/j.leukres.2006.05.019

Cited by 12 publications

(11 citation statements)

References 5 publications

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“…According to another Japanese study, there was a nearly quadratic relationship between plasma concentration and IM dose per square meter [21]. The authors suggested that more careful observation and treatment of side effects of IM may be needed especially for patients with CML who have a small physique [21]. However, in the present study, there was no statistical correlation between trough plasma IM level and BSA.…”

Section: Discussioncontrasting

confidence: 60%

“…Although BSA was not found to be a clinically significant determinant of the trough plasma IM level [10,11], the smaller body size of Asian patients as compared to Western patients might cause the difference in mean trough plasma IM level between Western and Asian patients with CML [20]. According to another Japanese study, there was a nearly quadratic relationship between plasma concentration and IM dose per square meter [21]. The authors suggested that more careful observation and treatment of side effects of IM may be needed especially for patients with CML who have a small physique [21].…”

Section: Discussionmentioning

confidence: 98%

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Trough plasma imatinib levels are correlated with optimal cytogenetic responses at 6 months after treatment with standard dose of imatinib in newly diagnosed chronic myeloid leukemia

Sohn

Kim³

et al. 2011

Leukemia & Lymphoma

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To investigate the correlation of trough imatinib mesylate (IM) levels with cytogenetic or molecular responses, we measured trough IM levels in patients with chronic myeloid leukemia, chronic phase (CML-CP), at 6 months of treatment with a standard dose of IM. Eighty-seven newly diagnosed patients with CML-CP were prospectively enrolled. Seventy-eight patients (89.7%) showed an optimal response (complete or partial cytogenetic response) at 6 months. Trough IM levels were 1378 + 725 ng/mL. When categorized into two groups, there was a statistically significant difference in numbers of patients with optimal and suboptimal responses at 6 months (group with 51000: 80.6% vs. 19.4%; 1000: 94.6% vs. 5.4%; p ¼ 0.032), and in numbers of patients with early major molecular response (early-MMR) and without MMR at 6 months (group with 51000: 3.2% vs. 96.8%; 1000: 21.4% vs. 78.6%; p ¼ 0.047). In conclusion, the incidence of optimal cytogenetic response or early-MMR in patients with CML-CP treated with IM for 6 months was significantly higher in those with a trough level of 1000 compared with those with a level of 51000. Dose escalation of IM can be one option in patients with CML showing suboptimal response or resistance to the standard dose of IM, especially with low trough plasma IM levels (51000 ng/mL).

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Section: Discussioncontrasting

confidence: 60%

Section: Discussionmentioning

confidence: 98%

Trough plasma imatinib levels are correlated with optimal cytogenetic responses at 6 months after treatment with standard dose of imatinib in newly diagnosed chronic myeloid leukemia

Sohn

Kim³

et al. 2011

Leukemia & Lymphoma

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“…In Japanese studies, grade 3 or 4 neutropenia and/or leukocytopenia occurred in 33.3% of patients, and grade 3 thrombocytopenia occurred in 12.8% of patients [29] . Given Asians' lower body weight and BSA, both Korean and Japanese doctors doubted whether 400 mg daily of imatinib was an optimal initial dose for Asian patients and proposed a lower dose [30][31][32][33][34] . We found that the imatinib plasma trough concentration of Chinese patients who received 400 mg imatinib daily was higher than that of Caucasian patients, which provides convincing proof that Asian patients with lower body weight or BSA need a lower dose of imatinib than Caucasian CML patients.…”

Section: Discussionmentioning

confidence: 99%

Imatinib plasma trough concentration and its correlation with characteristics and response in Chinese CML patients

Chen

et al. 2010

Acta Pharmacol Sin

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Aim: To investigate the pharmacokinetics of imatinib in Chinese chronic myelogenous leukemia (CML) patients. Methods: Fourty-six naïve Chinese CML patients treated with imatinib (400 and 600 mg daily, n=36 and 10, respectively) were recruited. The correlations of imatinib (400 mg) trough plasma concentrations (C mins ) with the patients' characteristics and responses were analyzed. Results: The overall mean (±SD, CV%) steady-state C mins for imatinib at 400 mg (n=36) and 600 mg (n=10) daily was 1325.61 ng/mL (±583.53 ng/mL; 44%) and 1550.90 ng/mL (±462.63 ng/mL; 30%), respectively, and no statistically significant differences were found between them (P=0.267). At 400 mg daily, female patients had significantly higher C mins than the male patients (P=0.048), and molecular responses were not correlated with imatinib C mins , but they were correlated with time elapsed before imatinib therapy. Conclusion:The results suggest that Chinese CML patients have higher imatinib C mins than their Caucasian counterparts and that the optimal initial imatinib dose for them requires further investigation.

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“…Horikoshi et al [6] suggested that the plasma level of imatinib increases in proportion to imatinib/BSA, and it has been proposed that trough plasma levels of 1 M , which is the effective concentration in vitro, was attained with 200 mg/ day of imatinib in Japanese patients with low BSA (mean 1.44 m 2 ) [5,6] . In our study, median BSA was 1.55 m 2 .…”

mentioning

confidence: 99%

“…There is evidence supporting that the effects of imatinib are dose dependent, and the plasma level of imatinib is proportional to imatinib/BSA [3,6] . Considering the above facts, clear differences in adverse events and effects may be assumed when a person with a height of 180 cm and a weight of 90 kg is prescribed the same dose as a person with a height of 155 cm and a weight of 45 kg.…”

mentioning

confidence: 99%

Reduced Dose of Imatinib for Patients with Chronic Myeloid Leukemia and Low Body Surface Area

et al. 2007

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Relationship between daily dose of imatinib per square meter and its plasma concentration in patients with chronic-phase chronic myeloid leukemia (CML)

Cited by 12 publications

References 5 publications

Trough plasma imatinib levels are correlated with optimal cytogenetic responses at 6 months after treatment with standard dose of imatinib in newly diagnosed chronic myeloid leukemia

Trough plasma imatinib levels are correlated with optimal cytogenetic responses at 6 months after treatment with standard dose of imatinib in newly diagnosed chronic myeloid leukemia

Imatinib plasma trough concentration and its correlation with characteristics and response in Chinese CML patients

Reduced Dose of Imatinib for Patients with Chronic Myeloid Leukemia and Low Body Surface Area

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