Management of imatinib-associated skin rash in a patient with metastatic gastrointestinal stromal tumor: a case report
© Blay; licensee BioMed Central Ltd. 2012
Received: 20 July 2012
Accepted: 23 November 2012
Published: 4 December 2012
Long-term continuous imatinib is recommended for adult patients with unresectable and/or metastatic KIT+ gastrointestinal stromal tumors (GIST) as long as the patient continues to benefit. In the adjuvant setting, recent findings indicate that patients at considerable risk of recurrence should receive at least 3 years of imatinib. Because imatinib is often administered for prolonged periods, proper management of imatinib-associated adverse events is crucial.
We report a 56-year-old man with metastatic KIT+ GIST of the liver who had Grade 3 imatinib intolerance (skin rash) when treatment was started. The rash was managed with antihistamine treatment (Dexchlorpheniramine maleate 4 mg per day) and several temporary (up to 2 weeks) dose interruptions. The patient’s skin rash partially improved, and he tolerated gradual reintroduction of imatinib over several months. The patient maintained imatinib 400 mg/d, and tolerated it during the 2 years when he was on antihistamine treatment. After 2 years, the patient continued imatinib therapy without having to take antihistamines. The patient responded according to RECIST 1.1 and Choi to imatinib treatment for his metastatic GIST (partial response). As of September, 2012, the patient has been on imatinib therapy for 131 months and remains progression free.
The results of this case report demonstrated that a patient with metastatic KIT+ GIST who was initially intolerant to imatinib maintained, and responded to imatinib therapy after treatment of an imatinib-associated adverse effect. These results suggest that initial intolerance to imatinib should not necessarily result in treatment discontinuation, as these adverse effects, when managed properly, may be tolerated and may decrease over time.
KeywordsGastrointestinal stromal tumor GIST Metastasis Imatinib mesylate Skin rash
Imatinib mesylate is approved for the treatment of adult patients with unresectable and/or metastatic KIT+ gastrointestinal stromal tumor (GIST) and for the adjuvant treatment of adult patients following resection of primary GIST . Current treatment guidelines recommend long-term continuous imatinib therapy in patients with advanced GIST and at least 12 months of adjuvant imatinib therapy for patients with a substantial risk of relapse [2, 3]. Recently reported results of the Scandinavian Sarcoma Group/Sarcoma Group of the Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) trial indicate that at least 3 years of adjuvant imatinib should be recommended in patients who have a considerable risk of recurrence after surgery . National Comprehensive Cancer Network and ESMO Guidelines have recently been updated, based on the results of the SSGXVIII/AIO trial, endorsing this recommendation [5, 6]. Because imatinib is often administered for prolonged periods of time, close monitoring and proper management of imatinib-associated adverse effects are crucial. Imatinib is generally well tolerated, although some patients have difficulty tolerating the standard starting dose of 400 mg/d. Here, we report on a patient with metastatic GIST who experienced skin toxicity in response to imatinib at the beginning of standard therapy. With prudent use of supportive care measures, the patient was able to continue imatinib therapy while remaining progression free for more than 10 years.
This case report demonstrates that a patient with metastatic GIST who has difficulty tolerating imatinib at the standard treatment initiation dose (400 mg/d) can be effectively managed with supportive care and dose adjustments in order to maintain response to treatment. This suggests that initial intolerance to imatinib should not necessarily result in treatment discontinuation, as some of these adverse effects, when managed properly, can be tolerated and may decrease over time.
Maintaining continuous drug administration at a sufficiently high dose is necessary for GIST patients to obtain clinical benefit from imatinib [8, 9]. However, adverse effects may reduce patient compliance and the clinical efficacy of the treatment. Although true imatinib intolerance is very rare, short-term intolerance and discomfort are not uncommon . The most frequently observed adverse effects, generally Grade 1 or 2, include edema, gastrointestinal effects (diarrhea or nausea/vomiting), skin rash, and fatigue. There are different strategies for managing each imatinib-related adverse effect . Skin rash, for example, which often occurs during the first few months of treatment initiation, can be managed with antihistamines and topical steroids . In patients with severe skin reactions, dose reduction or interruption of imatinib, and/or use of oral steroids may be required . Imatinib can be gradually reintroduced, and many patients, like the patient described in this case report, are eventually able to tolerate imatinib.
This patient has continued treatment with imatinib and has remained disease free for more than 10 years. This is one of the longest durations of imatinib treatment for advanced KIT+ GIST reported in the literature. Long-term follow-up results of a key trial in patients with metastatic/advanced GIST (B2222 study) recently showed that 18% of the 147 patients initially enrolled in the study remained on continuous imatinib at a median follow-up time of 9.4 years (maximum 9.9 years) . The results of this case report and the B2222 study support the long-term efficacy of imatinib for the treatment of patients with unresectable and/or metastatic KIT+ GIST.
In conclusion, early recognition and proper management of imatinib-associated adverse effects may help GIST patients maintain imatinib therapy and ultimately achieve optimal clinical efficacy.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Gastrointestinal stromal tumor
Scandinavian Sarcoma Group/Sarcoma Group of the Arbeitsgemeinschaft Internistische Onkologie.
Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. I thank Jinling Wu, MD, PhD, for her medical editorial assistance with this manuscript.
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