title: Pazopanib and soft-tissue sarcomas. Too toxic.
abstract: Soft-tissue sarcomas are rare tumours of mesenchymal origin. Patients with metastatic disease have a median survival of about 10 months. Doxorubicin, an anthracycline, is often used to reduce tumour volume, but it does not prolong overall survival. Pazopanib, a multiple tyrosine kinase inhibitor already marketed for kidney cancer, is now licensed for the treatment of certain metastatic soft-tissue sarcomas when chemotherapy fails or when the disease progresses despite adjuvant or neoadjuvant therapy. Clinical evaluation of pazopanib in this setting is based on a double-blind, randomised, placebo-controlled trial in 369 patients whose tumours had progressed despite at least one line of chemotherapy, based on an anthracycline. In this trial, pazopanib did not provide a statistically significant increase in overall survival. The median survival time was about 12 months. A statistically significant increase in median progression-free survival was observed (4.6 versus 1.6 months, an increase of 3 months), based mainly on radiological criteria. Pazopanib did not improve quality of life. The adverse effect profile includes cardiovascular, gastrointestinal and hepatic disorders, and palmoplantar erythrodysaesthesia. Serious adverse effects are frequent. Other life-threatening adverse effects observed in patients with soft-tissue sarcoma include pneumothorax (especially in case of pulmonary metastasis), heart failure, venous thrombosis, pulmonary embolism and hypothyroidism. In practice, given its lack of any proven impact on overall survival and its excessive toxicity, the use of pazopanib is not justified. It is better to focus on appropriate symptomatic care in order to preserve these patients' quality of life.
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D004311:Double-Blind Method; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D007191:Indazoles; D008099:Liver / Q000187:drug effects; D011030:Pneumothorax / Q000139:chemically induced; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011743:Pyrimidines / Q000009:adverse effects*; D011788:Quality of Life; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D013449:Sulfonamides / Q000009:adverse effects*
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib