The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Imatinib Plasma Levels Are Correlated With Clinical Benefit in Patients With Unresectable/Metastatic Gastrointestinal Stromal Tumors
Abstract
Purpose: To study the pharmacokinetics (PK) of imatinib (IM) in patients with advanced GI stromal tumors (GISTs) treated in a randomized phase II study and to explore the potential relationship between IM plasma levels and long-term clinical outcomes. Patients and Methods: Patients were randomly assigned to receive IM at 400 mg versus 600 mg daily. IM plasma levels were analyzed in a subset of patients (n = 73) for whom PK data on day 1 and at steady-state (SS, day 29) were available. IM PK was evaluated using a population PK approach. The relationship between IM plasma exposure and clinical outcome was explored by grouping patients into quartiles according to IM trough concentration (C min). The clinical outcome parameters evaluated include overall objective benefit rate (OOBR; complete response plus partial response plus stable disease) time to progression (TTP), and KIT genotyping. Results: IM PK exposure showed a high inter-patient variability, and clinical outcomes were correlated with IM trough levels at SS. The median TTP was 11.3 months for patients in the lowest C min quartile (Q1, < 1,110 ng/mL) compared with more than 30 months for Q2 to Q4 (P = .0029). OOBR was also inferior in Q1 patients. In patients with GIST with KIT exon 11 mutations (n = 39), the OOBR was 67% for Q1 patients versus 100% for all others (P = .001). Conclusion: In patients with advanced GIST, IM trough levels at SS were associated with clinical benefit. Patients with IM C min below 1,100 ng/mL showed a shorter TTP and lower rate of clinical benefit (OOBR). Further studies are justified to test whether monitoring IM plasma levels might optimize clinical outcomes for patients with GIST.
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Cites
Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors
Demetri, G. D., von Mehren, M., Blanke, C. D., Van den Abbeele, A. D., Eisenberg, B., Roberts, P. J., Heinrich, M. C., Tuveson, D. A., Singer, S., Janicek, M., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020461 · Cited by 4,389
Self-citationDiagnosis of gastrointestinal stromal tumors: A consensus approach
Fletcher, C. D. M., Berman, J. J., Corless, C., Gorstein, F., Lasota, J., Longley, B. J., Miettinen, M., O'Leary, T. J., Remotti, H., Rubin, B. P., et al. (2002) · Human Pathology · doi:10.1053/hupa.2002.123545 · Cited by 3,419
Kinase Mutations and Imatinib Response in Patients With Metastatic Gastrointestinal Stromal Tumor
Heinrich, M. C., Corless, C. L., Demetri, G. D., Blanke, C. D., von Mehren, M., Joensuu, H., McGreevey, L. S., Chen, C.-J., Van den Abbeele, A. D., Druker, B. J., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.04.190 · Cited by 2,299
Self-citationJoensuu, H., Roberts, P. J., Sarlomo-Rikala, M., Andersson, L. C., Tervahartiala, P., Tuveson, D., Silberman, S. L., Capdeville, R., Dimitrijevic, S., Druker, B., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200104053441404 · Cited by 2,037
Self-citationVerweij, J., Casali, P. G., Zalcberg, J., LeCesne, A., Reichardt, P., Blay, J.-Y., Issels, R., van Oosterom, A., Hogendoorn, P. C., Van Glabbeke, M., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17098-0 · Cited by 1,665
Miettinen, M., & Lasota, J. (2006) · Archives of Pathology & Laboratory Medicine · doi:10.5858/2006-130-1466-gstrom · Cited by 1,459
van Oosterom, A. T., Judson, I., Verweij, J., Stroobants, S., di Paola, E. D., Dimitrijevic, S., Martens, M., Webb, A., Sciot, R., Van Glabbeke, M., et al. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06535-7 · Cited by 1,264
Biology of Gastrointestinal Stromal Tumors
Corless, C. L., Fletcher, J. A., & Heinrich, M. C. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.05.140 · Cited by 1,224
Blanke, C. D., Demetri, G. D., von Mehren, M., Heinrich, M. C., Eisenberg, B., Fletcher, J. A., Corless, C. L., Fletcher, C. D. M., Roberts, P. J., Heinz, D., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.4403 · Cited by 996
Self-citationDebiec-Rychter, M., Sciot, R., Le Cesne, A., Schlemmer, M., Hohenberger, P., van Oosterom, A. T., Blay, J.-Y., Leyvraz, S., Stul, M., Casali, P. G., et al. (2006) · European Journal of Cancer · doi:10.1016/j.ejca.2006.01.030 · Cited by 892
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(2012) · Annals of Oncology · doi:10.1093/annonc/mds252 · Cited by 281
Metadata
- Authors
- Demetri, G. D., Wang, Y., Wehrle, E., Racine, A., Nikolova, Z., Blanke, C. D., Joensuu, H., & von Mehren, M.
- Venue
- Journal of Clinical Oncology
- Published
- 2009-07-01
- Volume
- 27
- Issue
- 19
- Pages
- 3141-3147
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2123346471
- Cited by
- 401
- References
- 27
- FWCI
- 34.26
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Imatinib Plasma Levels Are Correlated With Clinical Benefit in Patients With Unresectable/Metastatic Gastrointestinal Stromal Tumors. https://app.cochat.ai/papers/10.1200/jco.2008.20.4818
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- Demetri, G. D., Wang, Y., Wehrle, E., Racine, A., Nikolova, Z., Blanke, C. D., Joensuu, H., & von Mehren, M. (2009). Imatinib Plasma Levels Are Correlated With Clinical Benefit in Patients With Unresectable/Metastatic Gastrointestinal Stromal Tumors. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2008.20.4818
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