THE PATHOPHYSIOLOGICAL MECHANISM OF FLUID RETENTION IN ADVANCED CANCER-PATIENTS TREATED WITH DOCETAXEL, BUT NOT RECEIVING CORTICOSTEROID COMEDICATION

Aims Fluid retention is a phenomenon associated with taxoids. The prin cipal objective of this study was to investigate the pathophysiologica l mechanism of docetaxel-induced fluid retention in advanced cancer pa tients. Methods Docetaxel was administered as a 1 h intravenous infusi on every 3 weeks, for at least 4-6 consecutive cycles, to patients wit h advanced breast (n = 21) or ovarian (n = 3) carcinoma, who had recei ved previous chemotherapy, 21 for advanced disease. Phase II clinical trials have shown that 5 day corticosteroid comedication, starting 1 d ay before docetaxel infusion, significantly reduces the incidence and severity of fluid retention. This prophylactic corticosteroid regimen is currently recommended for patients receiving docetaxel but was not permitted in this study because of its possible interference with the underlying pathophysiology of the fluid retention. Results Fluid reten tion occurred in 21 of the 24 patients but was mainly mild to moderate , with only five patients experiencing severe fluid retention. Eightee n patients received symptomatic flavonoid treatment, commonly prescrib ed after the last cycle. Specific investigations for fluid retention c onfirmed a relationship between cumulative docetaxel dose and developm ent of fluid retention. Capillary filtration test analysis showed a tw o-step process for fluid retention generation, with progressive conges tion of the interstitial space by proteins and water starting between the second and the fourth cycle, followed by insufficient lymphatic dr ainage. Conclusions A vascular protector such as micronized diosmine h esperidine with recommended corticosteroid premedication and benzopyro nes may be useful in preventing and treating docetaxel-induced fluid r etention.