Current management of patients with gastrointestinal stromal tumor receiving the multitargeted tyrosine kinase inhibitor sunitinib

Pilotte, Amy Potter

doi:10.1185/03007995.2015.1045470

Cited by 3 publications

(5 citation statements)

References 70 publications

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“…Most adverse events experienced by patients treated with sunitinib were manageable and the majority of adverse events were grade 1 or 2, while grade 3 toxicities were recorded for 3 patients; 2 patients discontinued due to grade 2 adverse events. These findings are consistent with the well defined toxicity profile for sunitinib in patients with GIST and the finding that side effects can be managed with standard medical intervention and/or dose modification in this population [ 31 ]. The tolerability and safety in a small series of paediatric GIST patients [ 23 ] was not dissimilar to that observed in our series.…”

Section: Discussionsupporting

confidence: 87%

Treatment of gastrointestinal stromal tumours in paediatric and young adult patients with sunitinib: a multicentre case series

et al. 2017

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BackgroundGastrointestinal stromal tumours (GIST) are rarely encountered mesenchymal tumours of the gastrointestinal tract (1.5 people per 100,000/year) that are even more rarely seen in paediatric patients (1–2% of all cases). The standard treatment for advanced adult GIST is imatinib with sunitinib as a second-line option. Although the efficacy and tolerability of sunitinib in adults with GIST has been established, little is known of the profile of sunitinib in paediatric/young adult patients with GIST given the rarity of this disease.MethodsPaediatric/young adult patients aged up to 21 years with diagnosis of GIST who were treated with sunitinib were identified from retrospective records from three centres in Europe and the US. Most patients commenced sunitinib in a 6-week cycle, however, dosing could be reduced, delayed, changed to (or initiated with) a continuous schedule. Objective response (Response Evaluation Criteria In Solid Tumours [RECIST]) and adverse events were recorded.ResultsWe identified 9 paediatric/young adult patients (aged 11–21 years) with GIST who were treated with sunitinib de novo (n = 1) or following failure of imatinib (n = 8). Progressive disease was previously documented for all patients including 7 patients during imatinib therapy. Baseline patient and tumour profile characteristics showed a distinct profile (notably all were wild-type KIT/PDGFR) compared to that established for adults. Sunitinib treatment was associated with a best response of stable disease for 7 patients, with disease stabilisation lasting from 1 month to >73 months and a median progression free survival time of 15 months. There was some evidence of better disease control for sunitinib when compared to prior imatinib. Most adverse events with sunitinib were manageable and all were consistent with the known profile of the agent.ConclusionThe ability to draw firm conclusions from this case series is limited by the small number of patients and the use of retrospective data which is largely reflective of the rarity of this condition. However, our findings provide initial evidence of clinical benefit and a generally manageable toxicity profile for sunitinib when administered to paediatric/young adult patients with GIST, most of whom had documented progressive disease during prior imatinib treatment.

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Section: Discussionsupporting

confidence: 87%

Treatment of gastrointestinal stromal tumours in paediatric and young adult patients with sunitinib: a multicentre case series

et al. 2017

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“…When GIST progresses on imatinib or when the patient does not tolerate imatinib, the standard second-line treatment is sunitinib ( Yoo et al , 2013 ). The median PFS was 5.1 months on second-line sunitinib in a randomised trial ( Demetri et al , 2006 ) with a tendency for better PFS in patients with KIT exon 9 mutation compared with other genotypes ( Pilotte, 2015 ). However, patients eventually progress on sunitinib.…”

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confidence: 99%

Dovitinib in patients with gastrointestinal stromal tumour refractory and/or intolerant to imatinib

et al. 2017

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Background:This multicentre phase II trial (DOVIGIST) evaluated the antitumour activity of dovitinib as second-line treatment of patients with gastrointestinal stromal tumour (GIST) refractory to imatinib or who do not tolerate imatinib.Methods:Patients received oral dovitinib 500 mg day−1, 5 days on/2 days off, until GIST progression or unacceptable toxicity, with an objective to evaluate efficacy, assessed as the disease control rate (DCR) at 12 weeks. Tumour assessment and response to dovitinib therapy were evaluated by Response Evaluation Criteria In Solid Tumours (RECIST v1.1) and the Choi criteria. Secondary objectives included assessment of progression-free survival (PFS), safety and tolerability, and DCR at the end of treatment.Results:Thirty-eight of the 39 patients enrolled had histologically confirmed GIST. The DCR at 12 weeks was 52.6% (90% confidence interval (CI), 38.2–66.7%) meeting the preset efficacy criterion for the primary end point. The objective response rate (complete response+partial response) was 2.6% (1 of 38; 90% CI, 0.1–11.9%), and 5.3% (n=2; 90% CI, 0.9–15.7%) at the end of the study. The median PFS was 4.6 months (90% CI, 2.8–7.4 months). Dose interruption was required in 26 patients (66.7%), of which 18 (69.2%) were due to adverse events. The most frequently observed grade 3 adverse events included hypertension (n=7), fatigue (n=5), vomiting (n=4), hypertriglyceridaemia (n=4), and γ-glutamyltransferase increase (n=4).Conclusions:Dovitinib is an active treatment for patients with GIST who are intolerant to imatinib or whose GIST progresses on imatinib.

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Section: Use Of Second- and Third-line Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

“…[36] Sunitinib, as a second-line TKI, appears to cause fewer side effects that are easier to manage with specific medical support. [37] Currently, sunitinib can be used as a neoadjuvant treatment in locally advanced GISTs that are resistant to imatinib. [38] The third TKI, regorafenib, is another tyrosine kinase inhibitor with wide activity against KIT, PDGFRA, VEGFR, and BRAF, and was approved by the FDA in 2013 for third-line therapy for patients with GISTs refractory to both imatinib and sunitinib.…”

Section: Use Of Second-and Third-line Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

“…In addition, patients with GISTs harboring KIT exon 9 mutations are most likely to benefit from sunitinib treatment, while sunitinib is least useful for patients with PDGFRA mutations [36] . Sunitinib, as a second-line TKI, appears to cause fewer side effects that are easier to manage with specific medical support [37] . Currently, sunitinib can be used as a neoadjuvant treatment in locally advanced GISTs that are resistant to imatinib [38] …”

Section: Use Of Second- and Third-line Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

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The current state of chemotherapy for the treatment of gastrointestinal stromal tumors with different genotypes: a narrative review

Xiao

et al. 2021

J Bio-X Res

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the digestive system and are not sensitive to traditional chemotherapy. Therefore, historically, surgical resection was the only effective therapy. However, the emergence of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of GISTs, because they target c-Kit and PDGF receptor-a (PDGFRA), which are important in GIST development and progression. As research into c-Kit and PDGFRA continues, an increasing number of different TKIs are being used in the clinical setting. This review aims to discuss the current state of chemotherapy for the treatment of GISTs with different genotypes.

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Current management of patients with gastrointestinal stromal tumor receiving the multitargeted tyrosine kinase inhibitor sunitinib

Abstract: Care of patients with GIST can be enhanced through communication, support, knowledge, and education, with the goal of providing effective therapy and optimal symptom control.

Cited by 3 publications

References 70 publications

Treatment of gastrointestinal stromal tumours in paediatric and young adult patients with sunitinib: a multicentre case series

Treatment of gastrointestinal stromal tumours in paediatric and young adult patients with sunitinib: a multicentre case series

Dovitinib in patients with gastrointestinal stromal tumour refractory and/or intolerant to imatinib

The current state of chemotherapy for the treatment of gastrointestinal stromal tumors with different genotypes: a narrative review

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