☆ 4.5 Article

Antitumor effect and pharmacokinetics of intraperitoneal NK105, a nanomicellar paclitaxel formulation for peritoneal dissemination

CANCER SCIENCE (2012)

Journal

CANCER SCIENCE

Volume 103, Issue 7, Pages 1304-1310

Publisher

WILEY

DOI: 10.1111/j.1349-7006.2012.02274.x

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Ministry of Education, Culture, Sports, Science and Technology of Japan
Ministry of Health, Labour and Welfare of Japan

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Abstract

The intraperitoneal administration of paclitaxel has been shown to be a promising treatment strategy for peritoneal malignancy. The present study evaluated the effects of intraperitoneal administration of NK105, a paclitaxel-incorporating micellar nanoparticle, which has been shown to have a remarkable effect in a mouse model of gastric cancer. Intraperitoneal NK105 significantly reduced peritoneal tumors in vivo compared with the conventional paclitaxel formulation of paclitaxel solubilized in Cremophor EL and ethanol (PTX-Cre). Moreover, intraperitoneal NK105 significantly reduced the size of subcutaneously inoculated tumors, whereas no such effect was seen with PTX-Cre. Similar systemic toxic effects were observed following the intraperitoneal administration of both NK105 and PTX-Cre. Although NK105 disappeared rapidly almost within a day from the peritoneal cavity, the paclitaxel concentration in peritoneal nodules 4h after intraperitoneal administration was significantly higher in the NK105 group than in the PTX-Cre group (P<0.05), whereas there were no significant differences in liver paclitaxel concentrations between the two groups. We also evaluated the pharmacokinetics following intraperitoneal administration of NK105 and PTX-Cre. Serum paclitaxel concentrations 6, 12, 24, and 48h after the intraperitoneal administration of the drugs were significantly higher in the NK105 than the PTX-Cre group. Furthermore, the peak serum concentration was higher in the NK105 than PTX-Cre group (24100 +/- 3560 vs 108 +/- 25 similar to ng/mL, respectively; P<0.001), as was the area under the concentrationtime curve from 0 to 48h (191000 +/- 32100 vs 1500 +/- 108ng center dot h/mL, respectively; P<0.001). Therefore, intraperitoneal chemotherapy with nanoparticulate paclitaxel NK105 may offer a novel treatment strategy for improving drug delivery in gastric cancer with peritoneal dissemination because of enhanced drug penetration into peritoneal nodules and its prolonged presence in the systemic circulation. (Cancer Sci 2012; 103: 13041310)

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Intraperitoneal Paclitaxel Treatment for Patients with Pancreatic Ductal Adenocarcinoma with Peritoneal Dissemination Provides a Survival Benefit

Tomohisa Yamamoto, Sohei Satoi, So Yamaki, Daisuke Hashimoto, Mitsuaki Ishida, Tsukasa Ikeura, Satoshi Hirooka, Yuki Matsui, Shogen Boku, Shinji Nakayama, Koh Nakamaru, Nobuhiro Shibata, Utae Katsushima, Mitsugu Sekimoto

Summary: Pancreatic ductal adenocarcinoma (PDAC) with peritoneal dissemination is a highly lethal disease. Recent studies have shown promising activity of intraperitoneal chemotherapy with paclitaxel (i.p.-PTX) in PDAC patients with peritoneal dissemination. This retrospective comparative study compared the clinical efficacy of i.p.-PTX combined with systemic chemotherapy versus standard systemic chemotherapy in PDAC patients. The results show that i.p.-PTX therapy improved survival in PDAC patients with peritoneal dissemination, and conversion surgery enhanced survival in patients with favorable responses to chemotherapy.

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