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Japanese Journal of Cancer and Chemotherapy 2004-Apr

[Report of two cases with pleural effusion and ascites that responded dramatically to the combination of thalidomide, celecoxib, irinotecan, and CDDP infused in thoracic and abdominal cavities].

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Malignant pleural effusion (PE) and ascites are associated with highly symptomatic, advanced-stage cancers. These fluid accumulations cause severe symptoms such as abdominal distention, shortness of breath, cachexia, anorexia, and fatigue. Malignant PE and ascites have consistently been shown to indicate a poor prognosis in advanced-stage cancer patients, being associated with high morbidity and mortality. The efficacy of this treatment is variable and does not prolong the survival of cancer patients. Clearly, a more effective therapy for malignant PE and ascites is needed. Vascular permeability factor (VPF) from malignant ascites and PE have been hypothesized to be responsible for the fluid accumulations. In addition, malignant PE and ascites contain high levels of biologically active VEGF. VEGF was discovered as a potent angiogenesis stimulator and recognized to be VPF. Increased amounts of COX-2 have been detected in epithelial and stromal cells and COX-2 in mammary tissue is sufficient to induce cancer. It is suggested that COX-2 stimulates angiogenesis. A combination of molecular target inhibitors (thalidomide and celecoxib) and standard cytotoxic drugs appear to increase efficacy of each drug, decrease the side effects of cytotoxic drugs and prolong life.

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