EVALUATION OF THE ANTIPROSTAGLANDIN AGENT PIROXICAM IN 87 PATIENTS WITH ADVANCED CANCER

The well-documented in vitro antitumor effects of prostaglandins have not been evaluated as yet in clinical settings. Eighty-seven patients with advanced cancer unresponsive to other treatments were given oral piroxicam alone, for three months or more. Piroxicam was selected beca use of its long half-life. There were 14 objective responses (greater than 50 % according to WHO criteria), including 3 complete remissions (5 of 24 lung cancers, 3 of 13 metastasized sarcomas, 2 of 10 metastas ized renal cancers, and 4 other very advanced cancers : 1 mesothelioma , 1 endometrial cancer, 1 colorectal cancer, and 1 metastasized adenoc arcinoma from an unknown primary site). Overall survival ranged from 3 to 54 months. In addition, 28 patients had minor responses or prolong ed stabilization. Pain relief, return of body temperature to normal an d weight gain occurred in almost all patients, including those whose t umors failed to respond. Five patients (6 %) were withdrawn from the d rug because of a gastrointestinal ulcer. These unexpected results are biologically plausible. They may involve inhibition of immunosuppressi on, inhibition of angiogenesis, interference with nuclear transduction of mitogenic signals from membrane growth factor receptors, and/or in hibition of ornithine, decarboxylase activity. Prostaglandins PGE2 and PGF2 alpha, which are found in very large amounts in many tumors, see m to be the prostaglandins with the most marked stimulating effects on tumor growth. Antiprostaglandin treatment is inexpensive and can be c arried out on an outpatient basis. Further studies are warranted to ev aluate its role in combination with conventional chemotherapy and with redifferentiating and antiproliferative agents. This study is limited by the fact that piroxicam was used as rescue treatment. A prospectiv e evaluation is needed.