Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer.
Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer.
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DOI：
10.1038/bjc.2014.602
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发表时间：
2015-01-20
影响因子：
8.8
通讯作者：
Zucchetti, M.
中科院分区：
文献类型：
--
作者：
Ansaloni, L.;Coccolini, F.;Morosi, L.;Ballerini, A.;Ceresoli, M.;Grosso, G.;Bertoli, P.;Busci, L. M.;Lotti, M.;Cambria, F.;Pisano, M.;Rossetti, D.;Frigerio, L.;D'Incalci, M.;Zucchetti, M.
腹腔热化疗（HIPEC）被建议作为上皮性卵巢癌（EOC）伴腹膜癌转移的治疗选择。本研究旨在确定HIPEC期间顺铂（CDDP）和紫杉醇（PTX）联合给药的药代动力学。13名EOC女性接受了细胞减灭术（CRS）和HIPEC，CDDP和PTX。采集血液、腹膜灌注液和组织样本，通过高效液相色谱和基质辅助激光解吸电离成像质谱（IMS）测定药物暴露。灌流液中CDDP和PTX的平均最大浓度分别为24.8±10.4 μg ml−1和69.8±14.3 μg ml−1;血浆中分别为1.87±0.4 μg ml−1和0.055±0.009 μg ml−1。HIPEC结束时腹膜中CDDP和PTX的平均浓度分别为23.3±8.0 μg g−1和30.1±18.3 μg− 1 g −1。通过IMS测定，PTX渗透到腹膜壁中约为0.5 mm。4例患者记录了3-4级手术并发症，5例患者出现3级血液学并发症，2例患者出现4级血液学并发症。CRS后使用CDDP和PTX的HIPEC是可行的，发病率可接受，并具有良好的药代动力学特征：在腹膜组织中达到高药物浓度，全身暴露量低。需要更大规模的研究来证明其在腹腔镜手术后残留肿瘤患者中的疗效。
Hyperthermic intraperitoneal chemotherapy (HIPEC) is advised as a treatment option for epithelial ovarian cancer (EOC) with peritoneal carcinomatosis. This study was designed to define the pharmacokinetics of cisplatin (CDDP) and paclitaxel (PTX) administered together during HIPEC. Thirteen women with EOC underwent cytoreductive surgery (CRS) and HIPEC, with CDDP and PTX. Blood, peritoneal perfusate and tissue samples were harvested to determine drug exposure by high-performance liquid chromatography and matrix-assisted laser desorption ionization imaging mass spectrometry (IMS). The mean maximum concentrations of CDDP and PTX in perfusate were, respectively, 24.8±10.4 μg ml−1 and 69.8±14.3 μg ml−1; in plasma were 1.87±0.4 μg ml−1 and 0.055±0.009 μg ml−1. The mean concentrations of CDDP and PTX in peritoneum at the end of HIPEC were 23.3±8.0 μg g−1 and 30.1±18.3 μg−1g−1, respectively. The penetration of PTX into the peritoneal wall, determined by IMS, was about 0.5 mm. Grade 3–4 surgical complications were recorded in four patients, five patients presented grade 3 and two patients presented grade 4 hematological complications. HIPEC with CDDP and PTX after CRS is feasible with acceptable morbidity and has a favorable pharmacokinetic profile: high drug concentrations are achieved in peritoneal tissue with low systemic exposure. Larger studies are needed to demonstrate its efficacy in patients with microscopic postsurgical residual tumours in the peritoneal cavity.
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影响因子：
3
作者：
Fruscio, Robert;Lissoni, Andrea A.;Zucchetti, Massimo
通讯作者：
Zucchetti, Massimo
影响因子：
2.9
作者：
Cashin, P. H.;Ehrsson, H.;Mahteme, H.
通讯作者：
Mahteme, H.
影响因子：
2.8
作者：
Chua, Terence C.;Liauw, Winston;Morris, David L.
通讯作者：
Morris, David L.
影响因子：
2.1
作者：
Sugarbaker, Paul H.
通讯作者：
Sugarbaker, Paul H.
影响因子：
6.4
作者：
Uboldi, S.;Bernasconi, S.;D'Incalci, M.
通讯作者：
D'Incalci, M.