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. 2015 Jan 20;112(2):306-12.
doi: 10.1038/bjc.2014.602. Epub 2014 Dec 2.

Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer

L Ansaloni  1 , F Coccolini  1 , L Morosi  2 , A Ballerini  3 , M Ceresoli  1 , G Grosso  4 , P Bertoli  1 , L M Busci  4 , M Lotti  1 , F Cambria  5 , M Pisano  1 , D Rossetti  4 , L Frigerio  4 , M D'Incalci  2 , M Zucchetti  2
Affiliations

Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer

L Ansaloni et al. Br J Cancer. .

Abstract

Background: 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.

Methods: 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).

Results: 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(-1)g(-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.

Conclusions: 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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Figures

Figure 1
Figure 1
Mean concentrations of PTX (A) and CDDP (B) in plasma (●), perfusate (▪) and peritoneal tissue (▴) during HIPEC. The dashed line indicates the lowest cytotoxic concentration of these drugs.
Figure 2
Figure 2
PTX penetration in peritoneal tissue during HIPEC by MALDI imaging mass spectrometry.
See this image and copyright information in PMC

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