Abstract
A male 68 years hold patient was admitted to surgical ward for hemorrhagic shock. After CT scan detection of 6x5 cm neoformation of first jejunal loop, he was submitted to segmental resection and pathological diagnosis was gastrointestinal stromal tumor. The patient was defined as high-risk according to Takahashi criteria, but refused Imatinib adjuvant therapy. After 15 months of disease-free interval, he developed bilobar liver metastases. After treatment with Imatinib 400 mg he reported G3 hepatotoxicity resolved with temporary suspension, he continue low dose with stable disease. After liver progression, he resumed Imatinib full dose with disease stabilization for 9 months. After liver progression, second line Sunitinib 37,5 mg/day was started for four months with stable disease. After further liver and lymph node mediastinal progression he was treated for four months with Regorafenib with disease stabilization. Patient developed slow but inexorable progression of liver disease with severe abdominal pain resistant to opioid and was treated with authorized compassionate program comprising Cyclophosphamide 300 mg/sqm and Fluorouracil 500 mg/sqm on day 1 intravenously followed by Interleukin-2 4.5 MUI subcutaneously on days 3–6 and 17–20 every four weeks. After three cycles the patients obtained a relevant subjective improvement with partial response on mediastinal lymph node and liver stabilization. A substantial increase on neutrophil, lymphocytes, monocytes, platelets, T regulator cells count, and a decrease on platelets/lymphocytes, CD8/T regulator cells ratio, CD8, NK count and C-reactive protein value were observed after treatment compared to basal value. The toxicity was mild represented by fever G1, flue-like-syndrome G1 during the treatment. After four cycle of chemo-immunotherapy, the patient demonstrated progression of disease and died five months after treatment. Noteworthy is the temporal disease control with significant symptomatic improvement achieved for the first time with this chemo-immunotherapeutic combination in a patient with very advanced pretreated GIST.
Highlights
The growing interest resulting from the evidence that immune suppression plays an important role in the progression of disease in tumors has aroused much interest in the treatment of resistant tumors
The description of this case of heavily pre-treated GIST pays attention to a combined treatment that confirms the possibility of translating into practice the theoretical assumptions underlying immunosuppression
Adjuvant IM have positive impact on prognosis and survival in the intermediate-high risk, according to Miettinen prognostic score [4, 5]. After disease progression both after IM adjuvant and palliative therapy for advanced disease, different rates of primary or secondary resistance are observed depending on the type of mutation
Summary
The growing interest resulting from the evidence that immune suppression plays an important role in the progression of disease in tumors has aroused much interest in the treatment of resistant tumors. Thereafter from July 2012 to May 2014 he continues IM 300 mg/day with stable disease After liver progression, he resumed full dose IM from May 2014 to October 2015 obtaining a disease stabilization for 9 months. After further liver and lymph node mediastinal progression he was treated from June 2016 to October 2016 with standard dose of Regorafenib with disease stabilization. The patients after three cycles of therapy obtained a relevant subjective improvement with liver stabilization (Figure 1 D) and partial response on mediastinal lymph node (Figure 1 E-F). After four cycle of chemoimmunotherapy, the patient developed progression of disease and died five months after treatment
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