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Gastrointestinal Cancer
patients with exon 9 mutations than those with exon 11 mutations disease by increasing the dose. Neoadjuvant therapy has also been
under sunitinib therapy after failure or intolerance to imatinib.
35
As shown to be safe and beneficial as a palliative treatment. Many
previously discussed, there also appears to be a dose-dependent effect, questions still remain as to how imatinib therapy with GIST can be
where patients with exon 9 mutations receiving 800mg/day imatinib further improved and optimized—whether by dosing, early aggressive
have significantly improved response rates compared with those therapy, isolating factors that can predict clinical outcome, or
receiving 400mg/day, while those with exon 11 mutations do not individualized therapy based on mutational analysis. ■
experience any dose-dependent effect.
15,20,21
Mutational analysis may be
utilized to predict which patients have the best chance of responding to
Shreyaskumar R Patel, MD, is Medical Director of the
imatinib 800mg/day. Patients with KIT exon 11 mutations being treated
Sarcoma Center and a Tenured Professor of Medicine at
with the higher imatinib dose should be closely monitored, with the University of Texas MD Anderson Cancer Center in
treatment switching to next-generation TKIs considered in those who
Houston. His clinical research interests include systemic
therapy for sarcomas, gastrointestinal stromal tumours
experience disease progression.
(GISTs), and other tumors originating in bone and soft
tissues. Professor Patel has authored or co-authored more
Summary
than 100 articles in various peer-reviewed journals and has
been Section Editor for the Sarcoma Section of Current
The introduction of imatinib has drastically improved the outcome of
Oncology Reports since 2000. He has also authored or co-authored 15 book chapters.
patients with GISTs, especially those with advanced disease. Recent Professor Patel completed his medical graduation at Baroda Medical College in Baroda,
long-term data have shown that many patients who progress on the
India and pursued his training in medical oncology at the Mayo Clinic in Rochester.
conventional dose of imatinib are still able to achieve controllable
1. Hirota S, Isozaki K, Moriyama Y, et al., Gain-of-function tyrosine kinase: S0033, J Clin Oncol, 2008;26:626–32. 2007;245:347–52.
mutations of c-kit in human gastrointestinal stromal tumors, 14. Rankin C, von Mehren M, Blanke C, et al., Dose effect of 25. Fiore M, Palassini E, Fumagalli E, et al., Preoperative imatinib
Science, 1998;279:577–80. imatinib (IM) in patients (pts) with metastatic GIST – Phase III mesylate for unresectable or locally advanced primary
2. Heinrich MC, Corless CL, Demetri GD, et al., Kinase mutations Sarcoma Group Study S0033, Proc Am Soc Clin Oncol, gastrointestinal stromal tumors (GIST), Eur J Surg Oncol,
and imatinib response in patients with metastatic 2005;22(819s). 2009;35(7):739–45.
gastrointestinal stromal tumor, J Clin Oncol, 2003;21:4342–9. 15. Van Glabbeke MM, Owzar K, Rankin C, et al., Comparison of 26. Hohenberger P, Langer C, Pistorius S, et al., Indication and
3. DeMatteo RP, Lewis JJ, Leung D, et al., Two hundred two doses of imatinib for the treatment of unresectable or results of surgery following imatinib treatment of locally
gastrointestinal stromal tumors: recurrence patterns and metastatic gastrointestinal stromal tumors (GIST): A meta- advanced or metastatic GI stromal tumors (GIST), J Clin Oncol,
prognostic factors for survival, Ann Surg, 2000;231:51–8. analyis based on 1,640 patients (pts), J Clin Onc, 2007;25(18S): 2006;24(Suppl.): abstract 9500.
4. Blanke CD, Eisenberg BL, Heinrich MC, Gastrointestinal abstract 10004. 27. Raut CP, Posner M, Desai J, et al., Surgical management of
stromal tumors, Curr Treat Options Oncol, 2001;2:485–91. 16. Dileo P, Rankin CJ, Benjamin RS, et al., Incidence and reasons advanced gastrointestinal stromal tumors after treatment
5. Heinrich MC, Griffith DJ, Druker BJ, et al., Inhibition of c-kit for dose modification of standard-dose vs. high-dose imatinib with targeted systemic therapy using kinase inhibitors, J Clin
receptor tyrosine kinase activity by STI 571, a selective mesylate (IM) in the Phase III Intergroup Study S0033 of Oncol, 2006;24:2325–31.
tyrosine kinase inhibitor, Blood, 2000;96:925–32. patients (pts) with unresectable or metastatic gastrointestinal 28. Sym SJ, Ryu MH, Lee JL, et al., Surgical intervention following
6. Blanke CD, Demetri GD, von Mehren M , et al., Long-term stromal tumor (GIST), J Clin Oncol, 2005;23(Suppl.): abstract imatinib treatment in patients with advanced gastrointestinal
results from a randomized phase II trial of standard- versus 9032. stromal tumors (GISTs), J Surg Oncol, 2008;98:27–33.
higher-dose imatinib mesylate for patients with unresectable 17. Zalcberg JR, Verweij J, Casali PG, et al., Outcome of patients 29. Eisenberg BL, Harris J, Blanke CD, et al., Phase II trial of
or metastatic gastrointestinal stromal tumors expressing KIT, with advanced gastro-intestinal stromal tumours crossing neoadjuvant/adjuvant imatinib mesylate (IM) for advanced
J Clin Oncol, 2008;26:620–25. over to a daily imatinib dose of 800 mg after progression on primary and metastatic/recurrent operable gastrointestinal
7. van Oosterom AT, Judson IR, Verweij J, et al., Update of phase 400 mg, Eur J Cancer, 2005;41:1751–7. stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665,
I study of imatinib (STI571) in advanced soft tissue sarcomas 18. Park I, Ryu MH, Sym SJ, et al., Dose escalation of imatinib after J Surg Oncol, 2009;99:42–7.
and gastrointestinal stromal tumors: a report of the EORTC failure of standard dose in Korean patients with metastatic or 30. Blay JY, Le Cesne A, Ray-Coquard I, et al., Prospective
Soft Tissue and Bone Sarcoma Group, Eur J Cancer, 2002;38 unresectable gastrointestinal stromal tumor, Jpn J Clin Oncol, multicentric randomized phase III study of imatinib in patients
(Suppl. 5):S83–7. 2009;39:105–10. with advanced gastrointestinal stromal tumors comparing
8. Verweij J, Casali PG, Zalcberg J, et al., Progression-free survival 19. Demetri GD, Desai J, Fletcher JA, et al., SU11248, a multi- interruption versus continuation of treatment beyond 1 year:
in gastrointestinal stromal tumours with high-dose imatinib: targeted tyrosine kinase inhibitor, can overcome imatinib (IM) the French Sarcoma Group, J Clin Oncol, 2007;25:1107–13.
randomised trial, Lancet, 2004;364:1127–34. resistance caused by diverse genomic mechanisms in 31. Sciot R, Debiec-Rychter M, Daugaard S, et al., Distribution and
9. Blanke C, Joensuu H, Demetri G, et al., Long-term follow up of patients with metastatic gastrointestinal stromal tumor (GIST), prognostic value of histopathologic data and
advanced gastrointestinal stromal tumor (GIST) patients Proc Am Soc Clin Oncol, 2004;23:195, abstract 3001. immunohistochemical markers in gastrointestinal stromal
treated with imatinib mesylate, 2004 Gastrointestinal Cancers 20. Debiec-Rychter M, Sciot R, Le Cesne A, et al., KIT mutations tumours (GISTs): An analysis of the EORTC phase III trial of
Symposium, 2004; abstract 2. and dose selection for imatinib in patients with advanced treatment of metastatic GISTs with imatinib mesylate, Eur J
10. Verweij J, van Oosterom A, Blay JY, et al., Imatinib mesylate gastrointestinal stromal tumours, Eur J Cancer, 2006;42: Cancer, 2008;44:1855–60.
(STI-571 Glivec, Gleevec) is an active agent for gastrointestinal 1093–1103. 32. Blankstein ME, Rankin C, Fletcher C, et al., Clinical benefit of
stromal tumours, but does not yield responses in other soft- 21. Heinrich MC, Owzar K, Corless CL, et al., Correlation of kinase imatinib in patients (pts) with metastatic gastrointestinal
tissue sarcomas that are unselected for a molecular target. genotype and clinical outcome in the North American stromal tumors (GIST) negative for the expression of CD117in
Results from an EORTC Soft Tissue and Bone Sarcoma Group Intergroup Phase III Trial of imatinib mesylate for treatment of the S0033 trial, J Clin Oncol, 2005;23(Suppl.):818S, abstract 9010.
phase II study, Eur J Cancer, 2003;39:2006–11. advanced gastrointestinal stromal tumor: CALGB 150105 33. Corless CL, Fletcher JA, Heinrich MC, Biology of
11. Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al., Effect of the Study by Cancer and Leukemia Group B and Southwest gastrointestinal stromal tumors, J Clin Oncol, 2004;22:3813–25.
tyrosine kinase inhibitor STI571 in a patient with a metastatic Oncology Group, J Clin Oncol, 2008;26:5360–67. 34. Debiec-Rychter M, Dumez H, Judson I, et al., Use of c-KIT/
gastrointestinal stromal tumor, N Engl J Med, 2001;344:1052–6. 22. Loughrey MB, Mitchell C, Mann GB, et al., Gastrointestinal PDGFRA mutational analysis to predict the clinical response
12. Casali PG, Verweij J, Kotasek D, et al., Imatinib mesylate in stromal tumour treated with neoadjuvant imatinib, J Clin Pathol, to imatinib in patients with advanced gastrointestinal stromal
advanced Gastrointestinal Stromal Tumors (GIST): Survival 2005;58:779–81. tumours entered on phase I and II studies of the EORTC Soft
analysis of the Intergroup EORTC/ISG/AGITG randomized trial 23. Andtbacka RH, Ng CS, Scaife CL, et al., Surgical resection of Tissue and Bone Sarcoma Group, Eur J Cancer, 2004;40:689–95.
in 946 patients, Eur J Cancer Suppl, 2005;3:201, abstract 711. gastrointestinal stromal tumors after treatment with imatinib, 35. Heinrich MC, Maki RG, Corless CL, et al., Primary and
13. Blanke CD, Rankin C, Demetri GD, et al., Phase III randomized, Ann Surg Oncol, 2007;14:14–24. secondary kinase genotypes correlate with the biological and
intergroup trial assessing imatinib mesylate at two dose 24. DeMatteo RP, Maki RG, Singer S, et al., Results of tyrosine clinical activity of sunitinib in imatinib-resistant
levels in patients with unresectable or metastatic kinase inhibitor therapy followed by surgical resection for gastrointestinal stromal tumor, J Clin Oncol, 2008;26:5352–9.
gastrointestinal stromal tumors expressing the kit receptor metastatic gastrointestinal stromal tumor, Ann Surg,
64 US ONCOLOGY
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