June 20, 2008
renal cell carcinoma
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Department of Urology, Toyooka Hospital.
A 66-year-old man visited complaining of cough and sore throat. He had been exposed to asbestos 43 years ago. Chest X-ray revealed left pleural effusion and abnormal shadow in the right lung field. Chest computed tomography (CT) showed multiple enhanced nodules in the right pleural cavity. Abdominal CT showed a 3-cm enhanced tumor in the lower pole of the left kidney. Left radical nephrectomy was performed. Pathological diagnosis was renal cell carcinoma. Postoperatively pleural biopsy was performed by using thoracoscopy. White plaque was seen at the costal pleura and surface of lung. Pathological diagnosis was malignant pleural mesothelioma based on using mesothelium-associated antibodies: calretinin (+), CK5/6 (+), D2-40 (+), HBME-1 (+), TTF-1 (-), MOC31 (-), CEA (-). Combination therapy (extrapleural pneumonectomy, chemotherapy, and radiotherapy) was initiated. Malignant mesothelioma is a devastating neoplasm with a strong etiological relationship with asbestos exposure. The incidence is rising in industrialized countries, with the peak expected in the year 2020. However, renal cell carcinoma with malignant pleural mesothelioma is very rare and this is the 2nd case in the Japanese literature.
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May 11, 2008
renal cell carcinoma, renal cell, phase III clinical trial, advanced renal cell carcinoma, hormone therapy, Clinical trial, Lapatinib, carcinoma
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Department of Medical Oncology, Hôpital Saint André, CHU Bordeaux, 1 rue Jean Burguet, 33075 Bordeaux cedex, France. alain.ravaud@chu-bordeaux.fr
PURPOSE: Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2. PATIENTS AND METHODS: Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy–stratified by Karnofsky performance status and number of metastatic sites–were randomly assigned to lapatinib 1,250 mg daily or HT. The primary end point was time to progression (TTP); secondary end points included overall survival (OS), safety, and biomarker analyses. RESULTS: Four hundred sixteen patients were enrolled onto the study. Median TTP was 15.3 weeks for lapatinib versus 15.4 weeks for HT (hazard ratio [HR] = 0.94; P = .60), and median OS was 46.9 weeks for lapatinib versus 43.1 weeks for HT (HR = 0.88; P = .29). In a biomarker analysis of patients with EGFR-overexpressed tumors (3+ by immunohistochemistry [IHC]; n = 241) median TTP was 15.1 weeks for lapatinib versus 10.9 weeks for HT (HR = 0.76; P = .06), and median OS was 46.0 weeks for lapatinib versus 37.9 weeks for HT (HR = 0.69; P = .02). These results were confirmed by Cox regression analysis. No unexpected toxicities were observed; the most commonly reported drug-related adverse events (all grades) for lapatinib were rash (44%) and diarrhea (40%). CONCLUSION: Lapatinib was well tolerated with equivalent overall efficacy to HT in advanced RCC patients who had experienced disease progression while receiving cytokines, and the study supports that lapatinib prolonged OS relative to HT in patients with 3+ EGFR status determined by IHC.
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