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 principal objective of this study was to investigate the pathophysiological mechanism of docetaxel-induced fluid retention in advanced cancer patients. METHODS: Docetaxel was administered as a 1 h intravenous infusion every 3 weeks, for at least 4-6 consecutive cycles, to patients with advanced breast (n = 21) or ovarian (n = 3) carcinoma, who had received previous chemotherapy, 21 for advanced disease. Phase II clinical trials have shown that 5 day corticosteroid comedication, starting 1 day 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 retention occurred in 21 of the 24 patients but was mainly mild to moderate, with only five patients experiencing severe fluid retention. Eighteen patients received symptomatic flavonoid treatment, commonly prescribed after the last cycle. Specific investigations for fluid retention confirmed a relationship between cumulative docetaxel dose and development of fluid retention. Capillary filtration test analysis showed a two-step process for fluid retention generation, with progressive congestion of the interstitial space by proteins and water starting between the second and the fourth cycle, followed by insufficient lymphatic drainage. CONCLUSIONS: A vascular protector such as micronized diosmine hesperidine with recommended corticosteroid premedication and benzopyrones may be useful in preventing and treating docetaxel-induced fluid retention.

Prognostic factors and treatment of multiple myeloma: interest of a cyclic sequential chemohormonotherapy combining cyclophosphamide, melphalan, and prednisone.

1. A type 2 therapeutic trial consisting of the administration of monthly cycles of chemohormonotherapy, each cycle combining weekly sequences of mephalan, prednisone, cyclophosphamide, and prednisone, has been achieved in 20 stage II or III myeloma patients. Tolerance of this regimen in treated out-patients was found to be excellent. Preliminary data indicate that the better survival rate in patients treated by this regimen is still not reached at a 30-month follow-up examination by three other nonrandomized control groups of patients receiving continuous therapy with prednisone alone, prednisone + cyclophosphamide, or prednisone + melphalan. 2. Analysis of the main prognostic factors of the four trials indicates that a) IgG-type myelomas are associated with a better prognosis than IgA type; nonexcreting myelomas are associated with the best prognosis, while Bence Jones myelomas are associated with a prognosis as poor as that of the IgA type; b) tumor volume as well as renal insufficiency, at the time of diagnosis, are also prognosis factors; this study confirms the prognostic value of the recently proposed clinical staging system based on these parameters but outlines that 10% of the patients died from a cause not directly related to myeloma plasmocyte proliferation. 3. In conclusion, these results point out: a) the possible advantage of using two alkylating agents instead of one at the beginning of the disease; b) the need to classify multiple myeloma according to prognosis before attempting therapeutic trials.