Cyclophosphamide, Fluorouracil and subcutaneous Interleukin-2 in the treatment of advanced GIST: A Case Report

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.