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Various toxicities and compassionate use: case report A 10-year-old boy developed haematemesis, oesophagitis, ALT elevation, AST elevation and QTC prolongation during treatment with crizotinib on compassionate use basis, and myalgia during treatment with alectinib for metastatic medullary thyroid carcinoma (MTC) [routes, times to reaction onsets and outcomes not stated]. The boy was admitted with a 2-year history of progressive stridor and several days of acute worsening respiratory status. A detailed evaluation led to the diagnosis of metastatic MTC. Initially, he received empiric selpercatinib [LOXO-292], which he tolerated well with decreases calcitonin level. He continued selpercatinib for 14 days awaiting the next-generation sequencing resulted, which showed a copy number transition at the ALK locus between exons-18 and 19 present in the tumour only. The presence of an ALK rearrangement was confirmed. Selpercatinib was stopped, and he started receiving crizotinib solution 280 mg/m2 per dose twice daily, as part of a compassionate access protocol. His carcinoembryonic antigen (CEA) reduced by day 6 of the treatment with a reduction in calcitonin level. He experienced haematemesis concerning for oesophagitis on day 10 of crizotinib treatment, and he was intubated. The boy’s crizotinib dose was reduced. After 13 days of crizotinib and after 28 days of intubation, bronchoscopy revealed an improvement in subglottic compression and left vocal cord paralysis. He was then extubated. However, he developed grade 3 ALT and grade 2 AST elevation, along with grade 1 QTC prolongation due to crizotinib. Hence, crizotinib therapy was stopped. Three days later, the boy’s therapy with crizotinib was restarted at a reduced dose. He was discharged after a total 46 days of hospitalisation. A significant improvement in cancer was noted. At the first follow-up clinic visit, as he was able to swallow pills, his crizotinib therapy was switched to alectinib 350 mg/m2 per dose twice daily. He tolerated alectinib well except for grade 1 myalgia after the first week of treatment. He continued alectinib at full dose for >280 days with a good response. Hillier K, et al. A Novel ALK Fusion in Pediatric Medullary Thyroid Carcinoma. Thyroid 29: 1704-1707, No. 11, 14 Nov 2019. Available from: URL: http://doi.org/10.1089/ 803519056 thy.2019.0041

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Reactions 5 Dec 2020 No. 1833