Novinky v léčbě gastrointestinálního stromálního nádoru

Číslo: 5 / 2011 (Obsah)
Rubrika: Nové trendy ve farmakoterapii
Obor: Onkologie
Autoři: MUDr. Zdeněk Linke
prof. MUDr. Marta Kalousová, Ph.D.1
Autoři - působiště: Radioterapeuticko-onkologické oddělení FN Motol, Praha
1 Ústav biochemie a laboratorní diagnostiky VFN, Praha
Klíčová slova: GIST, přežití, imatinib, sunitinib, nilotinib
Citace: 1 Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002;347:472–80. 2 Verweij J, Casali PG, Zalcberg J, et al. Progression free survival in gastrointestinal stromal tumor with high a low dose imatinib: randomised trial. Lancet 2004;364:1127–34. 3 Rankin C, Von Mehren M, Blanke C, et al. Dose effect of imatinib in patients with metastatic GIST: Phase III Sarcoma Group Study S0033 (abstract 9005). Proc ASCO 2004;23:815. 4 Van Glabbeke M, Verweij J, Casali PG, et al. Initial and late resistance to imatinib in advanced gastro-intestinal stromal tumor are predicted by different prognostic factors, an EORTC-ISG-AGITG study. J Clin Oncol 2005;23:5795–804. 5 Blay JY, Le Cesne A, Ray-Coquard I, et al. 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. 6 Rios M, Lecesne A, Bui B, et al. Interruption of imatinib in GIST patients with advanced diasease after one year of treatment: Updated results of the prospective French Sarcoma Group randomized phase III trial on long term survival. J Clin Oncol 2007 ASCO Annual Meeting Proceedings Part I;25(18S, June 20 Supplement):abstract 10016. 7 Van Glabbeke MM, Owzar K, Rankin C, et al. Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST): A meta – metaanalysis based on 1.640 patients. J Clin Oncol 2007 ASCO Annual Meeting Proceedings Part I;25(18S, June 20 Supplement):abstract 10004. 8 Heindrich MC, Maki RG, Corless CL, et al. Sunitinib response in imatinib – resistant GIST correlates with KIT and PDGFR mutation status. J Clin Oncol 2006;24:9502. 9 Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006; 368:1329–38. 10 Van Oosterom AT, Dumez H, Desai J, et al. Combination signal transduction inhibition: A phase I/II trial of the oral m-TOR-inhibitor everolimus (E, RAD001) and imatinib mesylate in patients with gastrointestinal stromal tumors refractory to imatinib mesylate. J Clin Oncol 2004;22:3002. 11 Demetri GD. Inhibition of the heat shock protein 90 (Hsp90) chaperone with the novel agent IPI-504 to overcome resistance to tyrosine kinase inhibitors (TKIs) in metastatic GIST: Updated results of a phase I trial. J Clin Oncol 2007 ASCO Annual Meeting Proceedings Part I;25(18S, June 20 Supplement):abstract 10024. 12 Von Mehren M, Reichardt P, Casali PG, et al. A phase I study of AMN107 alone and in combination with imatinib in patients (pts) with imatinib-resistant gastrointestinal stromal tumors (GIST) – Study Update. J Clin Oncol 2007 ASCO Annual Meeting Proceedings Part I;25(18S, June 20 Supplement): abstract 10023. 13 Data on file, Novartis UK Ltd. Study No STI571B2222. Open, randomized, phase II study of Glivec in patients with unresectable or metastatic malignant gastrointestinal stromal tumors expressing c-kit. Report 15th December 2003. 14 Raut CP, De Matteo RP. Prognostic factors for primary GIST: prime time for personalized therapy? Ann Surg Oncol 2008;15:4–6. 15 De Matteo RP, Antonescu CR, Chadaram V, et al. Adjuvant imatinib mesylate in patients with primary high risk gastrointestinal stromal tumor (GIST) following complete resection: Safety results from the U.S. Intergroup Phase II trial ACOSOG Z9000. J Clin Oncol 2005 ASCO Annual Meeting Proceedings;23 Part I (16S, June 1 Supplement):abstract 9009. 16 De Matteo RP, Owzar K, Maki R, et al. Adjuvant imatinib mesylate increases recurrence free survival (RFS) in patients with completely resected localized primary gastrointestinal stromal tumor (GIST): North American Intergroup Phase III trial ACOSOG Z9001. J Clin Oncol ASCO Annual Meeting Proceedings Part I. 2007;25(Supplement):abstract 10079 17 Zhan WH. Efficacy and safety of adjuvant post-surgical therapy with imatinib in patients with high risk of relapsing GIST. J Clin Oncol 2007 ASCO Annual Meeting Proceedings Part I;25(18S, June 20 Supplement):abstract 10045. 18 Nilsson B, Sjolund K, Kindblom LC, et al: Adjuvant imatinib treatment improves recurrence-free survival in patients with high – risk gastrointestinal stromal tumours (GIST). Br J Cancer 2007;96:1656–8 19 Gold JS, Gonen MI, Maki RG, et al. A nomogram to predict recurrence after resection of primary gasatrointestinal stromal tumor (GIST). Gastorintestinal Cancer Symposium; Jan 19–21, 2007, Orlando. 20 Takahashi T, Nakajima K, Nishitani A, et al An enhanced risk-group stratification system for more practical prognostication of clinically malignant gastrointestinal stromal tumors. Int J Clin Oncol 2007;12:369–74. 21 Scandinavian Sarcoma Group. Study comparing 12 months versus 36 months of imatinib in the treatment of gastrointestinal stromal tumor (GIST). SSGXVIII/AIO. http:www.clinicaltrials.gov/ct/show/NCT00116935?order=1. Accessed October 25, 2007. 22 European Organisation for Research and Treatment of Cancer. Imatinib mesylate or observation only in treating patients who have undergone surgery for localized gastrointestinal stromal tumor – RORTC-62024. http:www.clinicaltrials.gov/ct/show/NCT00103168?order=1. Accessed October 25, 2007. 23 RTOG S-0132 protocol. A phase II trial of neoadjuvant/ adjuvant STI-571 (Gleevec NSC 716051) for primary and recurrent operable malignant GIST expressing the KIT receptor tyrosine kinase (CD117). www.rtog.org/members/protocols/s0132/s0132.pdf. Accessed October 3, 2007.

Souhrn

Pokročilý gastrointestinální stromální nádor (GIST) je vzácnější nádor gastrointestinálního traktu. Jeho pokročilá forma je velmi úspěšně léčena již řadu let imatinib mesylátem. Při selhání iniciální dávky imatinibu (400 mg/den) se jeho podávání neukončuje, nejčastěji je dávka zvýšena (většinou na 800 mg/den); teprve při další progresi se jako léčba 2. linie nasazuje sunitinib. Byla již získána data pro léčbu 3. linie – nilotinib; v rámci klinických studií se zkoušejí léky i pro vyšší linie léčby (IPI-504; inhibitory mTOR; sorafenib; dasatinib; masanitib aj.). Přitom riziko recidivy pokročilejších nádorů, které byly radikálně odstraněny, přesahuje u nejrizikovějších případů 80 %! Se zvětšováním nádoru a zvyšováním jeho mitotického indexu narůstá predikce pro užití imatinibu v adjuvantním podání u středně a vysoce rizikových GIST c-KIT-pozitivních. Zvyšuje se i význam primární lokalizace GIST – roste riziko recidivy zejména u primárních GIST duodena a rekta! Klinické studie U.S. Intergroup Phase II ACOSOG Z9000 a North American Intergroup Phase III ACOSOG Z9001 předpoklady přínosu roční ad-juvantní léčby imatinibem potvrdily a imatinib se stal doporučovaným standardem pro roční adjuvantní aplikaci u rizikovějších radikálně resekovaných GIST. Další posun v doporučení adjuvance imatinibem přinesla randomizovaná studie III. fáze SSGXVIII/AIO, jež potvrdila přínos nejen pro snížení výskytu relapsů, ale i pro prodloužení celkového přežití při adjuvantní léčbě imatinibem po dobu 36 měsíců oproti standardní 12měsíční adjuvanci.

Literatura

1
Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002;347:472–80. 2 Verweij J, Casali PG, Zalcberg J, et al. Progression free survival in gastrointestinal stromal tumor with high a low dose imatinib: randomised trial. Lancet 2004;364:1127–34. 3 Rankin C, Von Mehren M, Blanke C, et al. Dose effect of imatinib in patients with metastatic GIST: Phase III Sarcoma Group Study S0033 (abstract 9005). Proc ASCO 2004;23:815. 4 Van Glabbeke M, Verweij J, Casali PG, et al. Initial and late resistance to imatinib in advanced gastro-intestinal stromal tumor are predicted by different prognostic factors, an EORTC-ISG-AGITG study. J Clin Oncol 2005;23:5795–804. 5 Blay JY, Le Cesne A, Ray-Coquard I, et al. 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. 6 Rios M, Lecesne A, Bui B, et al. Interruption of imatinib in GIST patients with advanced diasease after one year of treatment: Updated results of the prospective French Sarcoma Group randomized phase III trial on long term survival. J Clin Oncol 2007 ASCO Annual Meeting Proceedings Part I;25(18S, June 20 Supplement):abstract 10016. 7 Van Glabbeke MM, Owzar K, Rankin C, et al. Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST): A meta – metaanalysis based on 1.640 patients. J Clin Oncol 2007 ASCO Annual Meeting Proceedings Part I;25(18S, June 20 Supplement):abstract 10004. 8 Heindrich MC, Maki RG, Corless CL, et al. Sunitinib response in imatinib – resistant GIST correlates with KIT and PDGFR mutation status. J Clin Oncol 2006;24:9502. 9 Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006; 368:1329–38.
10
Van Oosterom AT, Dumez H, Desai J, et al. Combination signal transduction inhibition: A phase I/II trial of the oral m-TOR-inhibitor everolimus (E, RAD001) and imatinib mesylate in patients with gastrointestinal stromal tumors refractory to imatinib mesylate. J Clin Oncol 2004;22:3002.
11
Demetri GD. Inhibition of the heat shock protein 90 (Hsp90) chaperone with the novel agent IPI-504 to overcome resistance to tyrosine kinase inhibitors (TKIs) in metastatic GIST: Updated results of a phase I trial. J Clin Oncol 2007 ASCO Annual Meeting Proceedings Part I;25(18S, June 20 Supplement):abstract 10024.
12
Von Mehren M, Reichardt P, Casali PG, et al. A phase I study of AMN107 alone and in combination with imatinib in patients (pts) with imatinib-resistant gastrointestinal stromal tumors (GIST) – Study Update. J Clin Oncol 2007 ASCO Annual Meeting Proceedings Part I;25(18S, June 20 Supplement): abstract 10023.
13
Data on file, Novartis UK Ltd. Study No STI571B2222. Open, randomized, phase II study of Glivec in patients with unresectable or metastatic malignant gastrointestinal stromal tumors expressing c-kit. Report 15th December 2003.
14
Raut CP, De Matteo RP. Prognostic factors for primary GIST: prime time for personalized therapy? Ann Surg Oncol 2008;15:4–6.
15
De Matteo RP, Antonescu CR, Chadaram V, et al. Adjuvant imatinib mesylate in patients with primary high risk gastrointestinal stromal tumor (GIST) following complete resection: Safety results from the U.S. Intergroup Phase II trial ACOSOG Z9000. J Clin Oncol 2005 ASCO Annual Meeting Proceedings;23 Part I (16S, June 1 Supplement):abstract 9009.
16
De Matteo RP, Owzar K, Maki R, et al. Adjuvant imatinib mesylate increases recurrence free survival (RFS) in patients with completely resected localized primary gastrointestinal stromal tumor (GIST): North American Intergroup Phase III trial ACOSOG Z9001. J Clin Oncol ASCO Annual Meeting Proceedings Part I. 2007;25(Supplement):abstract 10079
17
Zhan WH. Efficacy and safety of adjuvant post-surgical therapy with imatinib in patients with high risk of relapsing GIST. J Clin Oncol 2007 ASCO Annual Meeting Proceedings Part I;25(18S, June 20 Supplement):abstract 10045.
18
Nilsson B, Sjolund K, Kindblom LC, et al: Adjuvant imatinib treatment improves recurrence-free survival in patients with high – risk gastrointestinal stromal tumours (GIST). Br J Cancer 2007;96:1656–8
19
Gold JS, Gonen MI, Maki RG, et al. A nomogram to predict recurrence after resection of primary gasatrointestinal stromal tumor (GIST). Gastorintestinal Cancer Symposium; Jan 19–21, 2007, Orlando.
20
Takahashi T, Nakajima K, Nishitani A, et al An enhanced risk-group stratification system for more practical prognostication of clinically malignant gastrointestinal stromal tumors. Int J Clin Oncol 2007;12:369–74.
21
Scandinavian Sarcoma Group. Study comparing 12 months versus 36 months of imatinib in the treatment of gastrointestinal stromal tumor (GIST). SSGXVIII/AIO. http:www.clinicaltrials.gov/ct/show/NCT00116935?order=1. Accessed October 25, 2007.
22
European Organisation for Research and Treatment of Cancer. Imatinib mesylate or observation only in treating patients who have undergone surgery for localized gastrointestinal stromal tumor – RORTC-62024. http:www.clinicaltrials.gov/ct/show/NCT00103168?order=1. Accessed October 25, 2007.
23
RTOG S-0132 protocol. A phase II trial of neoadjuvant/ adjuvant STI-571 (Gleevec NSC 716051) for primary and recurrent operable malignant GIST expressing the KIT receptor tyrosine kinase (CD117). www.rtog.org/members/protocols/s0132/s0132.pdf. Accessed October 3, 2007.

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