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Published in: Clinical Sarcoma Research 1/2016

Open Access 01-12-2016 | Research

Clinical implications of repeated drug monitoring of imatinib in patients with metastatic gastrointestinal stromal tumour

Authors: Ivar Hompland, Øyvind Sverre Bruland, Kumari Ubhayasekhera, Jonas Bergquist, Kjetil Boye

Published in: Clinical Sarcoma Research | Issue 1/2016

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Abstract

Background

Imatinib mesylate (IM) is the preferred treatment for the majority of patients with metastatic gastrointestinal stromal tumour (GIST). Low trough IM concentration (Cmin) values have been associated with poor clinical outcomes in GIST patients. However, there are few studies of repeated measurements of IM levels, and therapeutic drug monitoring is not yet a part of routine clinical practice. This study was conducted to reveal clinical scenarios where plasma concentration measurement of IM trough level (Cmin) is advantageous.

Methods

Patients with advanced GIST receiving IM were included from January 2011 to April 2015. Heparin plasma was collected at each follow-up visit. Ninety-six samples from 24 patients were selected for IM concentration measurement. Associations between IM plasma concentration and clinical variables were analyzed by Students’ t test, univariate and multivariate linear regression analyses.

Results

The mean IM Cmin plasma concentrations for patients taking <400, 400 and >400 mg daily were 782, 1132 and 1665 ng/mL, respectively (p = 0.010). High IM Cmin levels were correlated with age, low body surface area, low haemoglobin concentration, low creatinine clearance, absence of liver metastasis and no prior gastric resection in univariate analysis. In multivariate analysis age, gastric resection and liver metastasis were included in the final model. Eight patients had disease progression during the study, and mean IM levels were significantly lower at time of progression compared to the previous measurement for the same patients (770 and 1223 ng/mL, respectively; p = 0.020).

Conclusions

Our results do not support repeated monitoring of IM levels on a routine basis in all patients. However, we have revealed clinical scenarios where drug measurement could be beneficial, such as for patients who have undergone gastric resection, suspicion of non-compliance, subjectively reported side effects, in elderly patients and at the time of disease progression.
Literature
1.
go back to reference Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D, Silberman S, Capdeville R, Dimitrijevic S, Druker B, Demetri GD. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. 2001;344:1052–6.CrossRefPubMed Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D, Silberman S, Capdeville R, Dimitrijevic S, Druker B, Demetri GD. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. 2001;344:1052–6.CrossRefPubMed
2.
go back to reference Blanke CD, Demetri GD, von Mehren M, Heinrich MC, Eisenberg B, Fletcher JA, Corless CL, Fletcher CDM, Roberts PJ, Heinz D, Wehre E, Nikolova Z, Joensuu H. Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol. 2008;26:620–5.CrossRefPubMed Blanke CD, Demetri GD, von Mehren M, Heinrich MC, Eisenberg B, Fletcher JA, Corless CL, Fletcher CDM, Roberts PJ, Heinz D, Wehre E, Nikolova Z, Joensuu H. Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol. 2008;26:620–5.CrossRefPubMed
3.
go back to reference Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–80.CrossRefPubMed Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–80.CrossRefPubMed
4.
go back to reference Demetri G, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts J, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347:472–80.CrossRefPubMed Demetri G, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts J, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347:472–80.CrossRefPubMed
5.
go back to reference Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay J-Y, Issels R, van Oosterom A, Hogendoorn PC, van Glabbeke M, Bertulli R, Judson I. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004;364:1127–34.CrossRefPubMed Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay J-Y, Issels R, van Oosterom A, Hogendoorn PC, van Glabbeke M, Bertulli R, Judson I. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004;364:1127–34.CrossRefPubMed
6.
go back to reference Demetri GD, Rankin CJ, Benjamin RS, et al. Long-term disease control of advanced gastrointestinal stromal tumors (GIST) with imatinib (IM): 10-year outcomes from SWOG phase III intergroup trial S0033. J Clin Oncol. 2014;32:5s (suppl; abstr 10508).CrossRef Demetri GD, Rankin CJ, Benjamin RS, et al. Long-term disease control of advanced gastrointestinal stromal tumors (GIST) with imatinib (IM): 10-year outcomes from SWOG phase III intergroup trial S0033. J Clin Oncol. 2014;32:5s (suppl; abstr 10508).CrossRef
7.
go back to reference The ESMO/European Sarcoma Network Working Group. Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl 3):iii21–6. The ESMO/European Sarcoma Network Working Group. Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl 3):iii21–6.
8.
go back to reference Peng B, Lloyd P, Schran H. Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44:879–94.CrossRefPubMed Peng B, Lloyd P, Schran H. Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44:879–94.CrossRefPubMed
9.
go back to reference Judson I, Ma P, Peng B, Verweij J, Racine A, di Paola ED, van Glabbeke M, Dimitrijevic S, Scurr M, Dumez H, van Oosterom A. Imatinib pharmacokinetics in patients with gastrointestinal stromal tumour: a retrospective population pharmacokinetic study over time. EORTC Soft Tissue and Bone Sarcoma Group. Cancer Chemother Pharmacol. 2004;55:379–86.CrossRefPubMed Judson I, Ma P, Peng B, Verweij J, Racine A, di Paola ED, van Glabbeke M, Dimitrijevic S, Scurr M, Dumez H, van Oosterom A. Imatinib pharmacokinetics in patients with gastrointestinal stromal tumour: a retrospective population pharmacokinetic study over time. EORTC Soft Tissue and Bone Sarcoma Group. Cancer Chemother Pharmacol. 2004;55:379–86.CrossRefPubMed
10.
go back to reference Delbaldo C, Chatelut E, Re M, Deroussent A, Seronie-Vivien S, Jambu A, Berthaud P, Le Cesne A, Blay JY, Vassal G. Pharmacokinetic-pharmacodynamic relationships of imatinib and its main metabolite in patients with advanced gastrointestinal stromal tumors. Clin Cancer Res. 2006;12:6073–8.CrossRefPubMed Delbaldo C, Chatelut E, Re M, Deroussent A, Seronie-Vivien S, Jambu A, Berthaud P, Le Cesne A, Blay JY, Vassal G. Pharmacokinetic-pharmacodynamic relationships of imatinib and its main metabolite in patients with advanced gastrointestinal stromal tumors. Clin Cancer Res. 2006;12:6073–8.CrossRefPubMed
11.
go back to reference Menon-Andersen D, Mondick JT, Jayaraman B, Thompson PA, Blaney SM, Bernstei M, Bond M, Champagne M, Fossler MJ, Barrett JS. Population pharmacokinetics of imatinib mesylate and its metabolite in children and young adults. Cancer Chemother Pharmacol. 2008;63:229–38.CrossRefPubMed Menon-Andersen D, Mondick JT, Jayaraman B, Thompson PA, Blaney SM, Bernstei M, Bond M, Champagne M, Fossler MJ, Barrett JS. Population pharmacokinetics of imatinib mesylate and its metabolite in children and young adults. Cancer Chemother Pharmacol. 2008;63:229–38.CrossRefPubMed
12.
go back to reference Schmidli H, Peng B, Riviere GJ, Capdeville R, Hensley M, Gathmann I, Bolton AE, Racine-Poon A. Population pharmacokinetics of imatinib mesylate in patients with chronic-phase chronic myeloid leukaemia: results of a phase III study. Br J Clin Pharmacol. 2005;60:35–44.CrossRefPubMedPubMedCentral Schmidli H, Peng B, Riviere GJ, Capdeville R, Hensley M, Gathmann I, Bolton AE, Racine-Poon A. Population pharmacokinetics of imatinib mesylate in patients with chronic-phase chronic myeloid leukaemia: results of a phase III study. Br J Clin Pharmacol. 2005;60:35–44.CrossRefPubMedPubMedCentral
13.
go back to reference Larson RA, Druker BJ, Guilhot F, O’Brien SG, Riviere GJ, Krahnke T, Gathmann I, Wang Y, IRIS (International Randomized Interferon vs STI571) Study Group. 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.CrossRefPubMed Larson RA, Druker BJ, Guilhot F, O’Brien SG, Riviere GJ, Krahnke T, Gathmann I, Wang Y, IRIS (International Randomized Interferon vs STI571) Study Group. 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.CrossRefPubMed
14.
go back to reference Yoo C, Ryu MH, Kang BW, Yoon SK, Ryoo BY, Chang HM, Lee JL, Beck MY, Kim TW, Kang YK. Cross-sectional study of imatinib plasma trough levels in patients with advanced gastrointestinal stromal tumors: impact of gastrointestinal resection on exposure to imatinib. J Clin Oncol. 2010;28:1554–9.CrossRefPubMed Yoo C, Ryu MH, Kang BW, Yoon SK, Ryoo BY, Chang HM, Lee JL, Beck MY, Kim TW, Kang YK. Cross-sectional study of imatinib plasma trough levels in patients with advanced gastrointestinal stromal tumors: impact of gastrointestinal resection on exposure to imatinib. J Clin Oncol. 2010;28:1554–9.CrossRefPubMed
15.
go back to reference Widmer N, Decosterd LA, Csajka C, Leyvraz S, Duchosal MA, Rosselet A, Rochat B, Eap CB, Henry H, Biollaz J, Buclin T. Population pharmacokinetics of imatinib and the role of alpha1-acid glycoprotein. Br J Clin Pharmacol. 2006;62:97–112.CrossRefPubMedPubMedCentral Widmer N, Decosterd LA, Csajka C, Leyvraz S, Duchosal MA, Rosselet A, Rochat B, Eap CB, Henry H, Biollaz J, Buclin T. Population pharmacokinetics of imatinib and the role of alpha1-acid glycoprotein. Br J Clin Pharmacol. 2006;62:97–112.CrossRefPubMedPubMedCentral
16.
go back to reference Demetri GD, Wang Y, Wehrle E, Racine A, Nikolova Z, Blanke CD, Joensuu H, von Mehren M. Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors. J Clin Oncol. 2009;27:3141–7.CrossRefPubMed Demetri GD, Wang Y, Wehrle E, Racine A, Nikolova Z, Blanke CD, Joensuu H, von Mehren M. Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors. J Clin Oncol. 2009;27:3141–7.CrossRefPubMed
17.
go back to reference Eechoute K, Fransson MN, Reyners AK, de Jong FA, Sparreboom A, van der Graaf TAW, Friberg LE, Schiavon G, Wiemer EAC, Verweij J, Loos WJ, Mathijssen RHJ, de Giorgi U. A long-term prospective population pharmacokinetic study on imatinib plasma concentrations in GIST patients. Clin Cancer Res. 2012;18:5780–7.CrossRefPubMed Eechoute K, Fransson MN, Reyners AK, de Jong FA, Sparreboom A, van der Graaf TAW, Friberg LE, Schiavon G, Wiemer EAC, Verweij J, Loos WJ, Mathijssen RHJ, de Giorgi U. A long-term prospective population pharmacokinetic study on imatinib plasma concentrations in GIST patients. Clin Cancer Res. 2012;18:5780–7.CrossRefPubMed
18.
go back to reference Bouchet S, Poulette S, Titier K, Moore N, Lassalle R, Abouelfath A, Italiano A, Chevreau C, Bompas E, Collard O, Duffaud F, Rios M, Cupissol D, Adenis A, Ray-Coquard I, Bouché O, Le Cesne A, Bui B, Blay JY, Molimard M. Relationship between imatinib trough concentration and outcomes in the treatment of advanced gastrointestinal stromal tumours in a real-life setting. Eur J Cancer. 2016;57:31–8.CrossRefPubMed Bouchet S, Poulette S, Titier K, Moore N, Lassalle R, Abouelfath A, Italiano A, Chevreau C, Bompas E, Collard O, Duffaud F, Rios M, Cupissol D, Adenis A, Ray-Coquard I, Bouché O, Le Cesne A, Bui B, Blay JY, Molimard M. Relationship between imatinib trough concentration and outcomes in the treatment of advanced gastrointestinal stromal tumours in a real-life setting. Eur J Cancer. 2016;57:31–8.CrossRefPubMed
19.
go back to reference Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, Blay JY, Leyvraz S, Stul M, Casali PG, Zalcberg J, Verweij J, van Glabbeke M, Hagemeijer A, Judson I. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer. 2006;42:1093–103.CrossRefPubMed Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, Blay JY, Leyvraz S, Stul M, Casali PG, Zalcberg J, Verweij J, van Glabbeke M, Hagemeijer A, Judson I. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer. 2006;42:1093–103.CrossRefPubMed
20.
go back to reference Park I, Ryu MH, Sym SJ, Lee SS, Jang G, Kim TW, Chang HM, Lee JL, Lee H, Kang YK. Dose escalation of imatinib after failure of standard dose in Korean patients with metastatic or unresectable gastrointestinal stromal tumor. Jpn J Clin Oncol. 2008;39:105–10.CrossRefPubMed Park I, Ryu MH, Sym SJ, Lee SS, Jang G, Kim TW, Chang HM, Lee JL, Lee H, Kang YK. Dose escalation of imatinib after failure of standard dose in Korean patients with metastatic or unresectable gastrointestinal stromal tumor. Jpn J Clin Oncol. 2008;39:105–10.CrossRefPubMed
21.
go back to reference Joensuu H, Trent JC, Reichardt P. Practical management of tyrosine kinase inhibitor-associated side effects in GIST. Cancer Treat Rev. 2011;37:75–88.CrossRefPubMed Joensuu H, Trent JC, Reichardt P. Practical management of tyrosine kinase inhibitor-associated side effects in GIST. Cancer Treat Rev. 2011;37:75–88.CrossRefPubMed
22.
go back to reference Mazzeo F, Duck L, Joosens E, Dirix L, Focan C, Forget F, De Geest S, Muermans K, van Lierde M-A, Macdonald K, Abraham I, De Grève J. Nonadherence to imatinib treatment in patients with gastrointestinal stromal tumors: the ADAGIO study. Anticancer Res. 2011;31:1407–9.PubMed Mazzeo F, Duck L, Joosens E, Dirix L, Focan C, Forget F, De Geest S, Muermans K, van Lierde M-A, Macdonald K, Abraham I, De Grève J. Nonadherence to imatinib treatment in patients with gastrointestinal stromal tumors: the ADAGIO study. Anticancer Res. 2011;31:1407–9.PubMed
23.
go back to reference Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41.CrossRefPubMed Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41.CrossRefPubMed
24.
go back to reference Gotta V, Widmer N, Montemurro M, Leyvraz S, Haouala A, Decosterd LA, Csajka C, Buclin T. Therapeutic drug monitoring of imatinib: Bayesian and alternative methods to predict trough levels. Clin Pharmacokinet. 2012;51:187–201.CrossRefPubMed Gotta V, Widmer N, Montemurro M, Leyvraz S, Haouala A, Decosterd LA, Csajka C, Buclin T. Therapeutic drug monitoring of imatinib: Bayesian and alternative methods to predict trough levels. Clin Pharmacokinet. 2012;51:187–201.CrossRefPubMed
25.
go back to reference Ubhayasekera SJKA, Aluthgedara W, Ek B, Bergquist J. Simultaneous quantification of imatinib and CGP74588 in human plasma by liquid chromatography-time of flight mass spectrometry (LC-TOF-MS). Anal Methods. 2016;8:3046–54.CrossRef Ubhayasekera SJKA, Aluthgedara W, Ek B, Bergquist J. Simultaneous quantification of imatinib and CGP74588 in human plasma by liquid chromatography-time of flight mass spectrometry (LC-TOF-MS). Anal Methods. 2016;8:3046–54.CrossRef
26.
go back to reference Skoglund K, Richter J, Olsson-Strömberg U, Bergquist J, Aluthgedara W, Ubhayasekera SJ, Vikingsson S, Svedberg A, Söderlund S, Sandstedt A, Johnsson A, Aagesen J, Alsenhed J, Hägg S, Peterson C, Lotfi K, Gréen H. In vivo cytochrome P450 3A isoenzyme activity and pharmacokinetics of imatinib in relation to therapeutic outcome in patients with chronic myeloid leukemia. Ther Drug Monit. 2016;38(2):230–238CrossRefPubMed Skoglund K, Richter J, Olsson-Strömberg U, Bergquist J, Aluthgedara W, Ubhayasekera SJ, Vikingsson S, Svedberg A, Söderlund S, Sandstedt A, Johnsson A, Aagesen J, Alsenhed J, Hägg S, Peterson C, Lotfi K, Gréen H. In vivo cytochrome P450 3A isoenzyme activity and pharmacokinetics of imatinib in relation to therapeutic outcome in patients with chronic myeloid leukemia. Ther Drug Monit. 2016;38(2):230–238CrossRefPubMed
27.
go back to reference Widmer N, Decosterd LA, Leyvraz S, Duchosal MA, Rosselet A, Debiec-Rychter M, Csajka C, Biollaz J, Buclin T. Relationship of imatinib-free plasma levels and target genotype with efficacy and tolerability. Br J Cancer. 2008;98:1633–40.CrossRefPubMedPubMedCentral Widmer N, Decosterd LA, Leyvraz S, Duchosal MA, Rosselet A, Debiec-Rychter M, Csajka C, Biollaz J, Buclin T. Relationship of imatinib-free plasma levels and target genotype with efficacy and tolerability. Br J Cancer. 2008;98:1633–40.CrossRefPubMedPubMedCentral
29.
go back to reference Noens L, van Lierde MA, de Bock R, Verhoef G, Zachée P, Berneman Z, Martiat P, Mineur P, van Eygen K, Macdonald K, de Geest S, Albrecht T, Abraham I. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood. 2009;113:5401–11.CrossRefPubMed Noens L, van Lierde MA, de Bock R, Verhoef G, Zachée P, Berneman Z, Martiat P, Mineur P, van Eygen K, Macdonald K, de Geest S, Albrecht T, Abraham I. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood. 2009;113:5401–11.CrossRefPubMed
30.
go back to reference Blay J-Y, Le Cesne A, Ray-Coquard I, Bui B, Duffaud F, Delbaldo C, Adenis A, Viens P, Rios M, Bompas E, Cupissol D, Guillemet C, Kerbrat P, Fayette J, Chabaud S, Berthaud P, Pérol D. Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol. 2007;25:1107–13.CrossRefPubMed Blay J-Y, Le Cesne A, Ray-Coquard I, Bui B, Duffaud F, Delbaldo C, Adenis A, Viens P, Rios M, Bompas E, Cupissol D, Guillemet C, Kerbrat P, Fayette J, Chabaud S, Berthaud P, Pérol D. Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol. 2007;25:1107–13.CrossRefPubMed
31.
go back to reference Le Cesne A, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Cioffi A, Emile J-F, Chabaud S, Pérol D, Blay J-Y. Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol. 2010;11:942–9.CrossRefPubMed Le Cesne A, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Cioffi A, Emile J-F, Chabaud S, Pérol D, Blay J-Y. Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol. 2010;11:942–9.CrossRefPubMed
32.
go back to reference Patrikidou A, Chabaud S, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Domont J, Perol D, Blay JY, le Cesne A. Influence of imatinib interruption and rechallenge on the residual disease in patients with advanced GIST: results of the BFR14 prospective French Sarcoma Group randomised, phase III trial. Ann Oncol. 2013;24:1087–93.CrossRefPubMed Patrikidou A, Chabaud S, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Domont J, Perol D, Blay JY, le Cesne A. Influence of imatinib interruption and rechallenge on the residual disease in patients with advanced GIST: results of the BFR14 prospective French Sarcoma Group randomised, phase III trial. Ann Oncol. 2013;24:1087–93.CrossRefPubMed
33.
go back to reference Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST). Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1640 patients. J Clin Oncol. 2010;28:1247–53.CrossRef Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST). Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1640 patients. J Clin Oncol. 2010;28:1247–53.CrossRef
34.
go back to reference Berglund E, Ubhayasekera SJKA, Karlsson F, Akcakaya P, Aluthgedara W, Åhlen J, Fröbom R, Nilsson IL, Lui WO, Larsson C, Zedenius J, Bergquist J, Bränström R. Intracellular concentration of the tyrosine kinase inhibitor imatinib in gastrointestinal stromal tumor cells. Anticancer Drugs. 2014;25:415–22.CrossRefPubMed Berglund E, Ubhayasekera SJKA, Karlsson F, Akcakaya P, Aluthgedara W, Åhlen J, Fröbom R, Nilsson IL, Lui WO, Larsson C, Zedenius J, Bergquist J, Bränström R. Intracellular concentration of the tyrosine kinase inhibitor imatinib in gastrointestinal stromal tumor cells. Anticancer Drugs. 2014;25:415–22.CrossRefPubMed
Metadata
Title
Clinical implications of repeated drug monitoring of imatinib in patients with metastatic gastrointestinal stromal tumour
Authors
Ivar Hompland
Øyvind Sverre Bruland
Kumari Ubhayasekhera
Jonas Bergquist
Kjetil Boye
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Clinical Sarcoma Research / Issue 1/2016
Electronic ISSN: 2045-3329
DOI
https://doi.org/10.1186/s13569-016-0062-2

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