Chinese consensus on management of tyrosine kinase inhibitor-associated side effects in gastrointestinal stromal tumors

Abstract

Tyrosine kinase inhibitors (TKIs) have improved the overall survival of patients with gastrointestinal stromal tumors (GISTs), but their side effects can impact dose intensity and, consequently, the clinical benefit. To date, no guideline or consensus has been published on the TKI-associated adverse reactions. Therefore, the Chinese Society of Surgeons for Gastrointestinal Stromal Tumor of the Chinese Medical Doctor Association organized an expert panel discussion involving representatives from gastrointestinal surgery, medical oncology, cardiology, dermatology, nephrology, endocrinology, and ophthalmology to consider the systemic clinical symptoms, molecular and cellular mechanisms, and treatment recommendations of GISTs. Here, we present the resultant evidence- and experience-based consensus to guide the management of TKI-associated side events in clinical practice.

Preoperative imatinib treatment in patients with locally advanced and metastatic/recurrent gastrointestinal stromal tumors

“…Besides, elimination of resistant lesion is believed in favor of reintroduction of IM management in the context that second-line therapies are frequently not as well-tolerated as that of IM. [ 24 – 26 ] Concerning synchronous/metachronous liver metastases, Y-Jiang Ye and colleagues found that combination of surgery with TKI treatment may be the most effective strategy for GIST patients with liver metastases. [ 27 ] It has been reported in a retrospective study shown that surgical resection of liver metastases and primary lesion in GIST patients combined with IM may be associated with prolonged OS.…”

Individualized Management of Blood Concentration in Patients with Gastrointestinal Stromal Tumors

“…56 The consensus in China suggests that reducing the dose of SU from 50 mg/d to 37.5 mg/d, can reduce the degree of neutropenia or thrombocytopenia. 57 In many solid tumors, increasing the dose will get better RFS and OS. A study in patients with mRCC or GIST confirmed that increasing the dose of SU can improve RFS, OS, and have a higher chance of antitumor response, but at the same time, it also increases the risk of adverse effects.…”

Imatinib-associated skin rash is related to treatment outcome in patients with unresectable and/or metastatic gastrointestinal stromal tumor

“…Imatinib is generally well tolerated in GIST patients, and most adverse effects do not need imatinib dose reduction or interruption (24,25). However, dose reduction is required by 40% of GIST patients, and the discontinuation rate of imatinib is as high as 49% in these patients (14,(25)(26)(27).…”

“…Maintaining a continuous and sufficient imatinib dose is important to achieve optimal clinical outcomes; therefore, adequate management of imatinib-associated adverse events is crucial (25,28). Skin rash commonly presenting as erythematous and maculopapular lesions occurs in up to 35% of GIST patients treated with imatinib, and approximately 10% of patients experience grades 3-4 skin rash (9,10,24). The underlying mechanism of imatinibrelated skin rash is still unclear, but based on the high frequency, it is believed to be due to the blockade of the c-kit protein, which is normally present in the skin, rather than hypersensitivity (28).…”