8145 Background: Based on our previous research we hypothesized that three important mechanisms underlie serosal effusions and extensive loco-regional edema of locally advanced malignancies: active vasodilation gradually evolving from local to regional aspects, and increased secretion of autacoids and aldosteron. Hence, vasoconstrictor drugs, autacoid antagonists, and spironolactone should oppose the process. Method: 25 patients (pts) with both tumors of various types and locations, and serosal effusions or locoregional edema for which antitumor treatments were inapplicable or had previously failed, were treated for 3–27 weeks with ergotamine 0.5 mg once daily and t.i.d. propranolol 20–40 mg, ibuprofen 200 mg, cyproheptadine 2 mg, ranitidine 150 mg, and spironolactone 25–50 mg. Pts with pain or on vasodilating drugs were excluded while dexametasone for anorexia and local wound care were allowed. Regression with =50% of either serosal effusions (i.e. at least doubling the interval of instrumental draining), regional edema, or the ulceration size /oozing was the criterion of efficacy. Results: The treatment was effective in 9 of 11 (81.8%) pts with serosal effusions (with renewed response of 4 re-treated recurrences after treatment discontinuation in 3 pts), and in 10 of 14 (71.4%) pts with local ulceration /oozing or edema extending to a whole limb. Complete remission was achieved in 9 pts, in three only after the addition of dexametasone 8 mg twice a week. No significant adverse effects occurred. Conclusions: This drug combination provides substantial palliation for loco-regional edema and serosal effusions related of malignancy. The additive effect of dexametasone deserves further exploration. No significant financial relationships to disclose.