Impact of L-carnitine on imatinib-related muscle cramps in patients with gastrointestinal stromal tumor.

Introduction Muscle cramps constitute one of the leading adverse events of imatinib, the standard first-line treatment for advanced gastrointestinal stromal tumor (GIST). This study aims to assess the impact of L-carnitine on relieving cramps in patients with GIST taking imatinib. Materials and methods We reviewed our prospective database for patients with GIST who took L-carnitine (500-mg tablet, 2-3 times daily) for muscle cramps in Asan Medical Center. The assessment tool included severity by the numeric rating scale (NRS), frequency, duration of cramps, and questionnaire for the disturbance in basic activities of daily living (ADL), instrumental ADL (iADL), outdoor activity, or sleeping before and after L-carnitine treatment. Results We examined 42 patients [median age: 60 (range: 17-81) years; males, 52.4%] who received L-carnitine for cramps on NRS ≥ 4 intensity during 2016-2017. In 83.3% of patients (n = 35), the NRS score declined to <4 points, with 8 patients (19.0%) experiencing complete disappearance of symptoms [median response time: 10 (range: 2-30) days]. Moreover, the median duration of each episode and frequency decreased from 5 to 2 min and from 30 to 3 times per month (P < 0.001), respectively. We observed substantial improvement in all quality-of-life aspects after L-carnitine (ADL, 73.2%-14.6%; iADL, 73.2%-17.1%; sleeping, 78.0%-22.0%; outdoor activity, 68.3%-17.1%; P < 0.001). ConclusionL-carnitine could effectively relieve imatinib-related muscle cramps in patients with GIST. Accordingly, a randomized phase 3 study is currently ongoing (NCT03426722).

Sunitinib as a second-line therapy for advanced GISTs after failure of imatinib: relationship between efficacy and tumor genotype in Korean patients.

BACKGROUND: To assess the efficacy and safety of sunitinib with regards to primary genotypes of tumor in Korean patients with advanced gastrointestinal stromal tumors (GISTs) who failed an initial therapy of imatinib. METHODS: Clinical data were collected from 88 consecutive patients with metastatic/unresectable GISTs treated with sunitinib at the Asan Medical Center. RESULTS: The median time-to-progression (TTP) and overall survival (OS) times were 7.1 months and 17.6 months, respectively. Of the 74 patients tested for KIT (exons 9, 11, 13, 17) and PDGFRA (exons 12 and 18), patients with KIT exon 9 mutant GIST (n = 11, 14.9%) showed numerically better clinical benefit (objective response or stable disease ≥ 24 weeks) rate (63.6% vs 46.8%, p = 0.504) and TTP (median 13.6 mo vs 6.9 mo, p = 0.631) than those with KIT exon 11 mutant GIST (n = 47, 63.5%). The most common grade 3/4 adverse events included neutropenia (34.1%), thrombocytopenia (33.0%) and hand-foot skin reaction (25.0%). CONCLUSIONS: Sunitinib is an effective and safe second-line therapy for Korean patients with advanced GIST. The superior efficacy of sunitinib against GISTs with KIT exon 9 mutations appears to be similar in Korean patients to Western experience although statistical significance was not secured.