Sunitinib for Taiwanese patients with gastrointestinal stromal tumor after imatinib treatment failure or intolerance

Chen, Yen‐Yang; Yeh, Chun‐Nan; Cheng, Chi‐Tung; Chen, Tsung-Wen; Rau, Kun‐Ming; Jan, Yi-Yin; Chen, Miin‐Fu

doi:10.3748/wjg.v17.i16.2113

Cited by 26 publications

(20 citation statements)

References 30 publications

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“…Dudeck et al (25) reported no CRs among 51 German patients with GIST. To the best of our knowledge, there have been three cases of CR following sunitinib as second-line chemotherapy for GIST in retrospective studies: 2/199 patients (1.0%) achieved CR in a Taiwanese study (26), and 1/48 patients (2.1%) achieved CR in a Chinese study (27). However, to our knowledge, there have been no individual case reports published anywhere worldwide; thus, the present study is the first case report showing CR following second-line sunitinib treatment for GIST.…”

Section: Discussionmentioning

confidence: 99%

Complete response to second-line chemotherapy with sunitinib of a gastrointestinal stromal tumor: A case report

Shirakawa

Hirata

Maemura

et al. 2017

Molecular and Clinical Oncology

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Abstract.Gastrointestinal stromal tumors (GISTs) are a type of sarcoma and the most common mesenchymal tumor of the gastrointestinal tract. Systemic chemotherapy is recommended for unresectable or metastatic GISTs. Imatinib, an oral multi-targeted receptor tyrosine kinase inhibitor, is an effective adjuvant chemotherapy for primary high-risk cases and palliative chemotherapy for unresectable or metastatic cases. For imatinib-resistant cases, second-line chemotherapy with sunitinib is recommended, as it has been demonstrated to result in a significantly longer median progression-free survival time and produce a higher response rate compared with placebo treatment. The current report describes the case of a 54-year-old woman who initially presented with persistent upper abdominal pain and anorexia. Upper gastrointestinal endoscopy and computed tomography revealed a submucosal tumor of the stomach with no apparent metastases. The patient underwent total radical gastrectomy and was diagnosed histologically with GIST with a high-risk of recurrence; therefore, adjuvant chemotherapy with imatinib was administered. However, multiple liver and lymph node metastases were subsequently detected, and the patient therefore received second-line sunitinib therapy. Following two cycles of sunitinib, the liver and lymph node metastases disappeared, and a complete response (CR) was achieved and sustained for at least 9 months. To the best of our knowledge, there have been no such cases of CR in previous prospective clinical trials examining the effects of sunitinib, and no other case reports of this worldwide. Thus, this study reports an extremely rare case of a patient with metastatic GIST who achieved CR with sunitinib as second-line chemotherapy. IntroductionGastrointestinal stromal tumors (GISTs) are a type of sarcoma and the most common mesenchymal tumor of the gastrointestinal tract. They arise from the interstitial cells of Cajal, typically occur in older individuals, and are most common in the stomach, followed by the small intestine (1). In Japan, GIST arises most frequently from the stomach, with a prevalence of 1-2 per 100,000 people (2). The majority of GISTs express the protein product of the KIT proto-oncogene, a transmembrane receptor tyrosine kinase (RTK), the activity of which would normally be regulated by the binding of its ligand (stem cell factor). KIT is positively expressed in ~95% of GISTs; therefore, if a tumor is positive for KIT on immunohistochemistry and its cells are morphologically consistent with GIST on hematoxylin and eosin staining, a diagnosis of GIST can be determined (3). CD34 is positively expressed in 70-80% of GIST cases, and CD34-positive staining can thus indicate a diagnosis of GIST, unless KIT expression is absent (4).As >40% of GISTs are clinically malignant and considered to be metastatic (1,5-7), systemic chemotherapy is indicated in a substantial proportion of GIST cases. Imatinib mesylate is an oral multi-targeted RTK inhibitor that is effective as adjuvant chemotherapy for primary...

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Section: Discussionmentioning

confidence: 99%

Complete response to second-line chemotherapy with sunitinib of a gastrointestinal stromal tumor: A case report

Shirakawa

Hirata

Maemura

et al. 2017

Molecular and Clinical Oncology

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“…Although the sound trials of sunitinib in GIST have mostly been performed in Western countries, retrospective series in both Taiwanese and Chinese population as well as a small prospective study in Chinese patients suggest similar efficacy and toxicity profile compared with Western population 23–25…”

Section: Development Of Sunitinib In Gist: From Bench To Bedsidementioning

confidence: 99%

Sunitinib in the treatment of gastrointestinal stromal tumor: patient selection and perspectives

Mulet-Margalef¹,

García‐del‐Muro²

2016

OTT

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Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. In advanced setting and after progression to imatinib, the multi-targeted receptor tyrosine kinase inhibitor sunitinib has clearly demonstrated a clinical benefit in terms of response rate and progression-free survival with an acceptable toxicity profile. The recommended schedule for sunitinib administration is 50 mg per day 4 weeks ON and 2 weeks OFF; however, potential alternative schedules are also reviewed in the present article. Several biomarkers have been explored to better select candidates for sunitinib therapy, such as the value of early changes in standardized uptake value assessed by positron emission tomography with 18F-fluorodeoxyglucose, circulating biomarkers, clinical biomarkers such as the appearance of arterial hypertension during treatment that correlates with better outcomes, and the GIST genotype. GISTs with KIT mutations at exon 9 and the so-called wild-type GISTs seem to better respond to sunitinib. Nonetheless, further investigation is required to confirm these findings as well as to understand the mechanisms of sunitinib resistance such as the development of new KIT mutations or conformational changes in KIT receptor.

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“…The phosphorylated receptor acts as a docking domain for intracellular adaptors that lead to the activation of a cascade of intracellular signal-transduction mediators, eventually leading to deoxyribonucleic acid synthesis, cell division, growth, proliferation, and migration 16. The Kit TKI sunitinib has shown a promising clinical profile for mastocytosis/mast cell leukemia, germ cell cancers, small-cell lung cancer, GISTs, acute myelogenous leukemia, neuroblastoma, melanoma, ovarian carcinoma, and breast carcinoma 12–17. In GIST, sunitinib against wild-type and exon 9-mutant Kit was superior to that of imatinib in vitro, whereas both drugs exhibited similar potency against Kit exon-11 mutant kinases 18.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…Other common laboratory abnormalities included increased serum creatinine (75.6%) and elevated alanine aminotransferase (53.5%). Chen et al reported that sunitinib-induced hypothyroidism was observed as a side effect in 12% of GIST patients 17. The molecular mechanisms of sunitinib-induced hypothyroidism are currently unknown, but one possible mechanism may be via inhibition of VEGFR and/or PDGFR in the thyroid tissue 81…”

Section: Sunitinib In Solid Cancersmentioning

confidence: 99%

Clinical response to sunitinib as a multitargeted tyrosine-kinase inhibitor (TKI) in solid cancers: a review of clinical trials

Kim¹,

Ding²,

Tian³

et al. 2014

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Angiogenesis is an integral process in carcinogenesis, and molecular inhibitors of angiogenic factors are currently being tested as treatments for cancer. Sunitinib is an oral multitargeted tyrosine-kinase inhibitor that blocks activation through the stem cell-factor receptor (Kit) and platelet-derived growth-factor receptor. Sunitinib has shown potent antitumor activity against several solid tumors, including renal cell carcinoma, gastrointestinal stromal tumors, and neuroendocrine tumors in several Phase II/III trials. Recently, sunitinib has been used to treat other solid cancers, such as lung cancer, pancreatic cancer, chondrosarcoma, esophageal cancer, bladder cancer, glioma, and aggressive fibromatosis, and also showed potential efficacy in progression-free survival and overall survival. In this review, we examine the efficacy of sunitinib as a molecular-targeted therapy in patients with different types of solid cancers.

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Sunitinib for Taiwanese patients with gastrointestinal stromal tumor after imatinib treatment failure or intolerance

Abstract: Sunitinib appears to be an effective treatment for Taiwanese with IM-resistant/intolerant GISTs and induced a sustained clinical benefit in more than 50% of Taiwanese advanced GIST patients.

Cited by 26 publications

References 30 publications

Complete response to second-line chemotherapy with sunitinib of a gastrointestinal stromal tumor: A case report

Complete response to second-line chemotherapy with sunitinib of a gastrointestinal stromal tumor: A case report

Sunitinib in the treatment of gastrointestinal stromal tumor: patient selection and perspectives

Clinical response to sunitinib as a multitargeted tyrosine-kinase inhibitor (TKI) in solid cancers: a review of clinical trials

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