The patient experienced significant side effects including fatigue, severe mouth soreness, decreased appetite, and hand-foot syndrome, necessitating dose reduction to oral sunitinib
malate at a dose of 37.5 mg/day after three cycles on the selleck compound initial dosage. Stable disease was achieved for approximately twelve months while on oral sunitinib. In April 2007, she had progression of disease in the form of a pathological fracture of the left humerus. Biopsy of the left humerus revealed a spindle cell sarcoma morphologically consistent with GIST metastasis, however Inhibitors,research,lifescience,medical immunohistochemical stains were negative for CD117 (c-KIT), CD34, and bcl-2. Sunitinib was discontinued preoperatively, and the patient underwent reconstruction of the left distal humerus. A CT of the abdomen and pelvis in May 2007 showed dramatic progression of liver metastases (Fig 3). Given the progression of
disease while being off sunitinib and in the absence of other standard of care treatment, she was restarted on oral sunitinib malate at a dose of 37.5 mg/day, on a schedule of Inhibitors,research,lifescience,medical 28 days on and 14 days off. In August 2007, she Inhibitors,research,lifescience,medical developed hard nodules in the subcutaneous area of the left upper extremity, concerning for tumor recurrence. CT scan of the left humerus revealed multiple soft tissue nodules scattered throughout the humerus (Fig 4). She continued sunitinib as systemic therapy Inhibitors,research,lifescience,medical and began local radiation therapy of the left humerus for palliation. Figure 3. Imaging of the abdomen by CT showing multiple large liver metastases. Figure 4. CT imaging of left humerus in the coronal
plane showing multiple metastatic soft tissue nodules. In October 2007, the patient was hospitalized for dyspnea, ascites, and lower extremity edema. Imaging showed further metastases to the peritoneum and lungs and bilateral Inhibitors,research,lifescience,medical pleural effusions (Fig 5). Despite two thoracenteses and pleurodesis, she had progressive symptoms and worsening lung nodules. Her respiratory failure was http://www.selleckchem.com/products/XL184.html rapidly progressive and she died in October 2007, approximately 55 months after her initial diagnosis. Figure 5. Chest CT image demonstrating multiple pulmonary nodules, compressive atelectasis and associated bilateral pleural effusions. Dacomitinib Due to unusual sites of metastases, a limited autopsy of the liver, lung and left arm tissue was performed after written consent from her power of attorney. The lung and liver metastatic lesions were morphologically consistent with GIST, and immunohistochemical stains were positive for CD117 (c-KIT). Tumor cells from the left arm subcutaneous nodule were morphologically suggestive of GIST but negative for CD117 by immunohistochemical staining. Molecular analysis demonstrated an in-frame deletion of 74450-74455 (6bp), or del559V-560V (or codons 559/560) in exon 11 of the KIT gene in sequences from metastases of the right lung, left lung, liver, and left arm subcutaneous nodule.