Pharmacokinetic–pharmacodynamic relationship of bosutinib in patients with chronic phase chronic myeloid leukemia
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- 作者：Poe-Hirr Hsyu (1)
Diane R. Mould (2)
Richard N. Upton (2)
Michael Amantea (1) - 关键词：Bosutinib ; Pharmacokinetic model ; Pharmacokinetic–pharmacodynamic analysis
- 刊名：Cancer Chemotherapy and Pharmacology
- 出版年：2013
- 出版时间：January 2013
- 年：2013
- 卷：71
- 期：1
- 页码：209-218
- 全文大小：607KB
- 参考文献：1. Puttini M, Coluccia AM, Boschelli F, Cleris L, Marchesi E, Donella-Deana A, Ahmed S, Redaelli S, Piazza R, Magistroni V, Andreoni F, Scapozza L et al (2006) In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl +neoplastic cells. Cancer Res 66:11314-1322 CrossRef
2. Golas JM, Arndt K, Etienne C, Lucas J, Nardin D, Gibbons J, Frost P, Ye F, Boschelli DH, Boschelli F (2003) SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res 63:375-81
3. Daud AI, Krishnamurthi SS, Saleh MN, Gitlitz BJ, Borad MJ, Gold PJ, Chiorean EG, Springett GM, Abbas R, Agarwal S, Bardy-Bouxin N, Hsyu PH et al (2012) Phase I study of bosutinib, a Src/Abl tyrosine kinase inhibitor, administered to patients with advanced solid tumors. Clin Cancer Res 18:1092-100 CrossRef
4. Cortes JE, Kantarjian HM, Brummendorf TH, Kim D-W, Turkina AG, Shen Z-X, Pasquini R, Khoury HJ, Arkin S, Volkert A, Besson N, Abbas R et al (2011) Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood 118:4567-576 CrossRef
5. Khoury HJ, Cortes JE, Kantarjian HM, Gambacorti-Passerini CB, Baccarani M, Kim DW, Zaritskey A, Countouriotis A, Besson N, Leip E, Kelly V, Brummendorf TH (2012) Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood 119:3403-412 CrossRef
6. Cortes JE, Kim Dong, Kantarjian HM, Brummendorf TH, Dyagil I, Griskevicus L, Malhotra H, Powell C, Gogat K, Countouriotis AM, Gambacorti-Passerini C (2012) Bosutinib versus imatinib in newly diagnosed chronic phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol (in press)
7. Hsyu P-H, Mould D, Abbas R, Pearce S, Amantea M (2011) A population pharmacokinetic model of bosutinib. Poster presented at: the AACR-EORTC-NCI molecular targets and cancer therapeutics conference; November 12-6, 2011; San Francisco, CA 2011. Abstract A195
8. Campone M, Bondarenko I, Brincat S, Hotko Y, Munster PN, Chmielowska E, Fumoleau P, Ward R, Bardy-Bouxin N, Leip E, Turnbull K, Zacharchuk C et al (2012) Phase II study of single-agent bosutinib, a Src/Abl tyrosine kinase inhibitor, in patients with locally advanced or metastatic breast cancer pretreated with chemotherapy. Ann Oncol 23:610-17 CrossRef
9. Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoli J, Paquette R, Cortes J, O’Brien S, Nicaise C, Bleickardt E, Blackwood-Chirchir MA (2006) Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 354:2531-541 CrossRef
10. Hochhaus A, Kantarjian HM, Baccarani M, Lipton JH, Apperley JF, Druker BJ, Facon T, Goldberg SL, Cervantes F, Niederwieser D, Silver RT, Stone RM et al (2007) Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood 109:2303-309 CrossRef
11. Kantarjian H, Pasquini R, Hamerschlak N, Rousselot P, Holowiecki J, Jootar S, Robak T, Khoroshko N, Masszi T, Skotnicki A, Hellmann A, Zaritsky A et al (2007) Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial. Blood 109:5143-150 CrossRef
12. Shah NP, Kantarjian HM, Kim DW, Rea D, Dorlhiac-Llacer PE, Milone JH, Vela-Ojeda J, Silver RT, Khoury HJ, Charbonnier A, Khoroshko N, Paquette RL et al (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. J Clin Oncol 26:3204-212 CrossRef
13. Kantarjian H, Giles F, Wunderle L, Bhalla K, O’Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A et al (2006) Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 354:2542-551 CrossRef
14. Kantarjian HM, Giles F, Gattermann N, Bhalla K, Alimena G, Palandri F, Ossenkoppele GJ, Nicolini FE, O’Brien SG, Litzow M, Bhatia R, Cervantes F et al (2007) Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood 110:3540-546 CrossRef
15. Quintas-Cardama A, Kantarjian H, Jones D, Nicaise C, O’Brien S, Giles F, Talpaz M, Cortes J (2007) Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failure. Blood 109:497-99 CrossRef
16. Garg RJ, Kantarjian H, O’Brien S, Quintas-Cardama A, Faderl S, Estrov Z, Cortes J (2009) The use of nilotinib or dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term follow-up. Blood 114:4361-368 CrossRef
17. Giles FJ, Abruzzese E, Rosti G, Kim DW, Bhatia R, Bosly A, Goldberg S, Kam GL, Jagasia M, Mendrek W, Fischer T, Facon T (2010) Nilotinib is active in chronic and accelerated phase chronic myeloid leukemia following failure of imatinib and dasatinib therapy. Leukemia 24:1299-301 CrossRef - 作者单位：Poe-Hirr Hsyu (1)
Diane R. Mould (2)
Richard N. Upton (2)
Michael Amantea (1)
1. Pfizer Inc, 10646 Science Center Drive, La Jolla, CA, USA
2. Projections Research Inc, Phoenixville, PA, USA - ISSN：1432-0843
文摘
Purpose Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor that has demonstrated manageable safety and high response rates in patients with chronic phase (CP) chronic myeloid leukemia (CML). The current analysis evaluated potential bosutinib pharmacokinetic–pharmacodynamic relationships. Methods Bosutinib exposure metrics at steady state were estimated from a previously developed population pharmacokinetic model. Safety and efficacy metrics were from two clinical studies of bosutinib 500?mg/day in patients with CP CML. Results The analysis included 749 patients (aged 18-1?years; mean weight, 75?kg; 54?% male). An exposure–response relationship was identified for the pooled incidence (but not severity) of diarrhea, with predicted probability ranging from 0.575 to 0.797 for the lowest and highest area under the curve bins, respectively; a weak relationship was also observed for the incidence of rash (predicted probability, 0.216-.419). There was no evidence of an exposure–response relationship for nausea, vomiting, neutropenia, thrombocytopenia, or elevated alanine and aspartate aminotransferases. Exposure–response relationships were observed in patients with newly diagnosed CP CML for complete cytogenetic response at 1?year (predicted probability, 0.476-.650), major molecular response at 1?year (0.238-.497), and cumulative complete hematologic response (CHR) at 1?year (0.605-.763). Patients with previously treated CP CML showed no exposure–response relationship for major cytogenetic response at 24?weeks (0.320); for CHR, higher bosutinib exposure was associated with a lower probability of response (0.926-.743). Conclusions The absence of exposure–response relationships for some safety and efficacy metrics may reflect bosutinib exposure metrics that exceeded the half-maximal inhibitory values and achieved a maximum effect.