Purpose: The aim of our study was to elucidate whether the fluid retention syndrome induced by docetaxel is caused by capillary protein leakage or by other mechanisms. Patients and Methods: Twenty-four patients with advanced or metastatic non-small-cell lung cancer (NSCLC; 23 patients) or metastatic head and neck cancer (one patient) were included on this prospective, nonrandomized trial. Docetaxel 100 mg/m(2) was administered every 3 weeks with 5 days of dexamethasone prophylaxis to avoid hypersensitivity reactions and edema formation. Transcapillary forces, ie, colloid osmotic pressure of plasma (COPpl) and interstitial fluid (COPint) and interstitial hydrostatic pressure (P-int), were measured before the start of treatment and after total docetaxel doses of 200 and 500 mg/m(2) by means of the well-documented wick and wick-in-needle methods. Body weight, degree of edema, blood pressure, and heart rare and hemoglobin, hematocrit, albumin, and total protein values were registered in parallel. Results: After a total docetaxel dose of 200 mg/m(2), COPpl, COPint, and hemoglobin, hematocrit, albumin, and total protein values had decreased significantly; P-int and body weight were unchanged; and only mild edema was observed. These findings suggest a plasma volume increase followed by enhanced fluid filtration to the interstitium. After a cumulative docetaxel dose of 500 mg/m(2), the COPpl continued to decrease significantly, but COPint remained unchanged despite a significant increase in mean body weight and edema formation. These observations support the theory of a capillary protein leakage. Conclusion: Docetaxel appears to induce an initial enhancement of fluid filtration followed by a capillary protein leakage that leads to edema formation. (C) 1998 by American Society of Clinical Oncology.