Semb K A, Aamdal S, Oian P
Department of Oncology, The Norwegian Radium Hospital, Oslo.
J Clin Oncol. 1998 Oct;16(10):3426-32. doi: 10.1200/JCO.1998.16.10.3426.
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.
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/m2 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 (Pint), were measured before the start of treatment and after total docetaxel doses of 200 and 500 mg/m2 by means of the well-documented wick and wick-in-needle methods. Body weight, degree of edema, blood pressure, and heart rate and hemoglobin, hematocrit, albumin, and total protein values were registered in parallel.
After a total docetaxel dose of 200 mg/m2, COPpl, COPint, and hemoglobin, hematocrit, albumin, and total protein values had decreased significantly; Pint 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/m2, 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.
Docetaxel appears to induce an initial enhancement of fluid filtration followed by a capillary protein leakage that leads to edema formation.
我们研究的目的是阐明多西他赛诱导的液体潴留综合征是由毛细血管蛋白渗漏还是其他机制引起的。
24例晚期或转移性非小细胞肺癌(NSCLC;23例患者)或转移性头颈癌(1例患者)纳入了这项前瞻性、非随机试验。每3周给予多西他赛100mg/m²,并给予5天的地塞米松预防,以避免过敏反应和水肿形成。在治疗开始前以及多西他赛总剂量达到200mg/m²和500mg/m²后,通过记录完善的灯芯法和针内灯芯法测量跨毛细血管压力,即血浆胶体渗透压(COPpl)、组织液胶体渗透压(COPint)和组织液静水压(Pint)。同时记录体重、水肿程度、血压、心率以及血红蛋白、血细胞比容、白蛋白和总蛋白值。
多西他赛总剂量达到200mg/m²后,COPpl、COPint以及血红蛋白、血细胞比容、白蛋白和总蛋白值均显著下降;Pint和体重未改变,仅观察到轻度水肿。这些发现提示血浆容量增加,随后液体向组织间隙的滤过增强。多西他赛累积剂量达到500mg/m²后,COPpl继续显著下降,但尽管平均体重和水肿形成显著增加,COPint仍未改变。这些观察结果支持毛细血管蛋白渗漏的理论。
多西他赛似乎首先诱导液体滤过增强,随后导致毛细血管蛋白渗漏,进而形成水肿。