Phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumours of the stomach

被引：74

作者：

Kurokawa, Yukinori ^{[1
]}

Yang, Han-Kwang ^{[2
,3
]}

Cho, Haruhiko ^{[4
]}

Ryu, Min-Hee ^{[5
]}

Masuzawa, Toru ^{[6
]}

Park, Sook Ryun ^{[5
]}

Matsumoto, Sohei ^{[7
]}

Lee, Hyuk-Joon ^{[2
,3
]}

Honda, Hiroshi ^{[8
]}

Kwon, Oh Kyoung ^{[9
]}

Ishikawa, Takashi ^{[10
]}

Lee, Kyung Hee ^{[11
]}

Nabeshima, Kazuhito ^{[12
]}

Kong, Seong-Ho ^{[2
,3
]}

Shimokawa, Toshio ^{[13
]}

Yook, Jeong-Hwan ^{[14
]}

Doki, Yuichiro ^{[1
]}

Im, Seock-Ah ^{[15
,16
]}

Hirota, Seiichi ^{[17
]}

Hahn, Seokyung ^{[18
]}

Nishida, Toshirou ^{[19
]}

Kang, Yoon-Koo ^{[5
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Gastroenterol Surg, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan

[2] Seoul Natl Univ, Coll Med, Dept Surg, 101 Daehak Ro, Seoul 03080, South Korea

[3] Seoul Natl Univ, Coll Med, Canc Res Inst, 101 Daehak Ro, Seoul 03080, South Korea

[4] Kanagawa Canc Ctr, Dept Surg, Asahi Ku, 2-3-2 Nakao, Yokohama, Kanagawa 2418515, Japan

[5] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, 88 Olymp Ro 43 Gil, Seoul 05505, South Korea

[6] Osaka Police Hosp, Dept Surg, Tennoji Ku, 10-31 Kitayamacho, Osaka 5430035, Japan

[7] Nara Med Univ, Dept Surg, 840 Shijo Cho, Kashihara, Nara 6348522, Japan

[8] Sendai Open Hosp, Dept Surg, Miyagino Ku, 5-22-1 Tsurugaya, Sendai, Miyagi 9830824, Japan

[9] Kyungpook Natl Univ, Med Ctr, Gastr Canc Ctr, 807 Hoguk Ro, Daegu 41404, South Korea

[10] Niigata Univ, Dept Surg, 1-754 Asahimachidouri, Niigata 9518520, Japan

[11] Yeungnam Med Ctr, Dept Hematooncol, 170 Hyeonchung Ro, Daegu 42415, South Korea

[12] Tokai Univ, Dept Surg, 143 Shimokasuya, Isehara, Kanagawa 2591193, Japan

[13] Wakayama Med Univ, Clin Study Support Ctr, 811-1 Kimiidera, Wakayama 6418510, Japan

[14] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Surg, 88 Olymp Ro 43 Gil, Seoul 05505, South Korea

[15] Seoul Natl Univ, Coll Med, Dept Internal Med, 101 Daehak Ro, Seoul 03080, South Korea

[16] Seoul Natl Univ, Coll Med, Canc Res Inst, 101 Daehak Ro, Seoul 03080, South Korea

[17] Hyogo Coll Med, Dept Surg Pathol, 1-1 Mukogawacho, Nishinomiya, Hyogo 6638501, Japan

[18] Seoul Natl Univ Hosp, Med Res Collaborating Ctr, 101 Daehak Ro, Seoul 03080, South Korea

[19] Nat Canc Ctr Hosp, Chuo Ku, 5-1-1 Tsukiji, Tokyo 1040045, Japan

来源：

BRITISH JOURNAL OF CANCER | 2017年 / 117卷 / 01期

关键词：

GIST; imatinib; neoadjuvant; preoperative; stomach; gastric; OF-FUNCTION MUTATIONS; ADJUVANT IMATINIB; RANDOMIZED-TRIAL; MESYLATE; RISK; RECURRENCE; PROGNOSIS; PATHOLOGY; RESECTION; THERAPY;

D O I：

10.1038/bjc.2017.144

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Gastrointestinal stromal tumours (GISTs) with high-risk features have poor prognosis even if adjuvant treatment is given. Neoadjuvant imatinib may increase the cure rate by shrinking large GISTs and preserve organ function. Methods: We conducted an Asian multinational phase II study for patients with gastric GISTs >= 10 cm. Patients received neoadjuvant imatinib (400 mg/day) for 6-9 months. The primary end point was R0 resection rate. Results: A total of 56 patients were enroled in this study. In the full analysis set of 53 patients, neoadjuvant imatinib for >= 6 months was completed in 46 patients. Grade 3-4 neutropenia and rash occurred in 8% and 9%, respectively, but there were no treatment-related deaths. The response rate by RECIST was 62% (95% CI, 48-75%). The R0 resection rate was 91% (48/53) (95% CI, 79-97%). Preservation of at least half of the stomach was achieved in 42 of 48 patients with R0 resection. At the median follow-up time of 32 months, 2-year overall and progression-free survival rates were 98% and 89%, respectively. Conclusions: Neoadjuvant imatinib treatment for 6-9 months is a promising treatment for large gastric GISTs, allowing a high R0 resection rate with acceptable toxicity.

引用

页码：25 / 32

页数：8

共 30 条

[1] We should desist using RECIST, at least in GIST [J].

Benjamin, Robert S. ;

Choi, Haesun ;

Macapinlac, Homer A. ;

Burgess, Michael A. ;

Patel, Shreyaskumar R. ;

Chen, Lei L. ;

Podoloff, Donald A. ;

Charnsangavej, Chuslip .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (13) :1760-1764

[2] 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].

Blanke, Charles D. ;

Demetri, George D. ;

von Mehren, Margaret ;

Heinrich, Michael C. ;

Eisenberg, Burton ;

Fletcher, Jonathan A. ;

Corless, Christopher L. ;

Fletcher, Christopher D. M. ;

Roberts, Peter J. ;

Heinz, Daniela ;

Wehre, Elisabeth ;

Nikolova, Zariana ;

Joensuu, Heikki .

JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (04) :620-625

[3] Time to Definitive Failure to the First Tyrosine Kinase Inhibitor in Localized GI Stromal Tumors Treated With Imatinib As an Adjuvant: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Intergroup Randomized Trial in Collaboration With the Australasian Gastro-Intestinal Trials Group, UNICANCER, French Sarcoma Group, Italian Sarcoma Group, and Spanish Group for Research on Sarcomas [J].

Casali, Paolo G. ;

Le Cesne, Axel ;

Velasco, Andres Poveda ;

Kotasek, Dusan ;

Rutkowski, Piotr ;

Hohenberger, Peter ;

Fumagalli, Elena ;

Judson, Ian R. ;

Italiano, Antoine ;

Gelderblom, Hans ;

Adenis, Antoine ;

Hartmann, Jorg T. ;

Duffaud, Florence ;

Goldstein, David ;

Broto, Javier M. ;

Gronchi, Alessandro ;

Dei Tos, Angelo P. ;

Marreaud, Sandrine ;

van der Graaf, Winette T.A. ;

Zalcberg, John R. ;

Litiere, Saskia ;

Blay, Jean-Yves .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (36) :4276-4283

[4] Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: Proposal of new computed tomography response criteria [J].

Choi, Haesun ;

Charnsangavej, Chuslip ;

Faria, Silvana C. ;

Macapinlac, Homer A. ;

Burgess, Michael A. ;

Patel, Shreyaskumar R. ;

Chen, Lei L. ;

Podoloff, Donald A. ;

Benjamin, Robert S. .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (13) :1753-1759

[5] Pathologic and Molecular Features Correlate With Long-Term Outcome After Adjuvant Therapy of Resected Primary GI Stromal Tumor: The ACOSOG Z9001 Trial [J].

Corless, Christopher L. ;

Ballman, Karla V. ;

Antonescu, Cristina R. ;

Kolesnikova, Violetta ;

Maki, Robert G. ;

Pisters, Peter W. T. ;

Blackstein, Martin E. ;

Blanke, Charles D. ;

Demetri, George D. ;

Heinrich, Michael C. ;

von Mehren, Margaret ;

Patel, Shreyaskumar ;

McCarter, Martin D. ;

Owzar, Kouros ;

DeMatteo, Ronald P. .

JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (15) :1563-U61

[6] KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours [J].

Debiec-Rychter, Maria ;

Sciot, Raf ;

Le Cesne, Axel ;

Schlemmer, Marcus ;

Hohenberger, Peter ;

van Oosterom, Allan T. ;

Blay, Jean-Yves ;

Leyvraz, Serge ;

Stul, Michel ;

Casali, Paolo G. ;

Zalcberg, John ;

Verweij, Jaap ;

Van Glabbeke, Martine ;

Hagemeijer, Anne ;

Judson, Ian .

EUROPEAN JOURNAL OF CANCER, 2006, 42 (08) :1093-1103

[7] Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST) [J].

DeMatteo, Ronald P. ;

Gold, Jason S. ;

Saran, Lisa ;

Goenen, Mithat ;

Liau, Kui Hin ;

Maki, Robert G. ;

Singer, Samuel ;

Besmer, Peter ;

Brennan, Murray F. ;

Antonescu, Cristina R. .

CANCER, 2008, 112 (03) :608-615

[8] Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial [J].

DeMatteo, Ronald P. ;

Ballman, Karla V. ;

Antonescu, Cristina R. ;

Maki, Robert G. ;

Pisters, Peter W. T. ;

Demetri, George D. ;

Blackstein, Martin E. ;

Blanke, Charles D. ;

von Mehren, Margaret ;

Brennan, Murray F. ;

Patel, Shreyaskumar ;

McCarter, Martin D. ;

Polikoff, Jonathan A. ;

Tan, Benjamin R. ;

Owzar, Kouros .

LANCET, 2009, 373 (9669) :1097-1104

[9] Prolonged Therapy with Imatinib Mesylate before Surgery for Advanced Gastrointestinal Stromal Tumor Results of a Phase II Trial [J].

Doyon, C. ;

Sideris, L. ;

Leblanc, G. ;

Leclerc, Y. E. ;

Boudreau, D. ;

Dube, P. .

INTERNATIONAL JOURNAL OF SURGICAL ONCOLOGY, 2012, 2012

[10] New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].

Eisenhauer, E. A. ;

Therasse, P. ;

Bogaerts, J. ;

Schwartz, L. H. ;

Sargent, D. ;

Ford, R. ;

Dancey, J. ;

Arbuck, S. ;

Gwyther, S. ;

Mooney, M. ;

Rubinstein, L. ;

Shankar, L. ;

Dodd, L. ;

Kaplan, R. ;

Lacombe, D. ;

Verweij, J. .

EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247

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