High Penetration of Paclitaxel in Abdominal Wall of Rabbits after Hyperthermic Intraperitoneal Administration of Nab-Paclitaxel Compared to Standard Paclitaxel Formulation

Catena, Fausto; Acocella, Fabio; Morosi, Lavinia; Brizzola, Stefano; Ghiringhelli, Matteo; Ceresoli, Marco; Davoli, Enrico; Ansaloni, Luca; D’Incalci, Maurizio; Zucchetti, Massimo

doi:10.1007/s11095-017-2132-4

Cited by 23 publications

(16 citation statements)

References 39 publications

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“…Preliminary data from animal models seem to confirm the potential of IP ABP administration. Coccolini and coworkers compared HIPEC with either ABP or cremophor-based paclitaxel in a rabbit model and found that ABP penetrated up to 0.63 mm in the (healthy) peritoneal wall, while the standard formulation was not detectable in the peritoneum [8]. We have recently demonstrated that IP ABP results in significant antitumor efficacy in a mouse xenograft model of peritoneal metastasis from ovarian origin (Carlier et al, manuscript in preparation).…”

Section: Resultsmentioning

confidence: 99%

“…Preclinical studies have demonstrated that IP administration of nano-and microsized formulations of paclitaxel results in superior antitumor activity against mouse ovarian cancer (OC) xenografts compared to intravenous administration [7]. In a recent study using an HIPEC model in the rabbit, peritoneal tissue concentrations after IP ABP were five times higher compared to IP Taxol [8]. IP catheter-based delivery of Abraxane was recently studied in a phase I clinical trial in advanced carcinomatosis patients [9].…”

Section: Introductionmentioning

confidence: 99%

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Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis – a phase I first-in-human study

Sande

Graversen

Hübner

et al. 2018

Pleura and Peritoneum

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BackgroundNanoparticles hold considerable promise for aerosol-based intraperitoneal delivery in patients with carcinomatosis. Recently, results from preclinical and early clinical trials suggested that albumin-bound paclitaxel (ABP, Abraxane™) may result in superior efficacy in the treatment of peritoneal metastases (PM) compared to the standard solvent-based paclitaxel formulation (Taxol™). Here, we propose a phase I study of pressurized intraperitoneal aerosol chemotherapy (PIPAC) using ABP in patients with upper Gastrointestinal, breast, or ovarian cancer.MethodsEligible patients with advanced, biopsy-proven PM from ovarian, breast, gastric, hepatobiliary, or pancreatic origin will undergo three PIPAC treatments using ABP with a 4-week interval. The dose of ABP will be escalated from 35 to 140 mg/m² using a Bayesian approach until the maximally tolerated dose is determined. The primary end point is dose-limiting toxicity. Secondary analyses include surgical morbidity, non-access rate, pharmacokinetic and pharmacodynamic analyses, quality of life, and exploratory circulating biomarker analyses.DiscussionABP holds considerable promise for intraperitoneal aerosol delivery. The aim of this study is to determine the dose level for future randomized phase II trials using ABP in PIPAC therapy.Trial registrationThis trial is registered as EudraCT: 2017-001688-20 and Clinicaltrials.gov: NCT03304210.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis – a phase I first-in-human study

Sande

Graversen

Hübner

et al. 2018

Pleura and Peritoneum

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“…Simulations based on population pharmacokinetic modeling showed that the tissue distribution of nab-PTX was more dependent upon an active transport mechanism, i.e., endothelial transcytosis for drug distribution into tissues than that of sb-PTX [8]. A preclinical study in rabbits, in which nab-PTX and sb-PTX were intraperitoneally administered, showed that nab-PTX penetrated the peritoneum tissue better than sb-PTX [9]. Moreover, a previous preclinical study that compared intravenous administration of nab-PTX with intraperitoneal administration of sb-PTX in a peritoneal metastasis mouse model reported that intravenous nab-PTX demonstrated an equivalent effect of reducing ascites and peritoneal tumors to intraperitoneal sb-PTX at equal doses [10].…”

Section: Discussionmentioning

confidence: 99%

Peritoneal metastasis as a predictive factor for nab-paclitaxel in patients with pretreated advanced gastric cancer: an exploratory analysis of the phase III ABSOLUTE trial

et al. 2018

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Background In the ABSOLUTE trial, weekly nanoparticle albumin-bound paclitaxel (w-nab-PTX) showed non-inferiority to weekly solvent-based paclitaxel (w-sb-PTX) for overall survival (OS). Thus, w-nab-PTX might be an option for secondline chemotherapy in advanced gastric cancer (AGC). However, predictive factors for efficacies of these agents have not been evaluated. Methods Patients previously enrolled in the ABSOLUTE trial were divided into apparent peritoneal metastasis group (PM group) and no apparent peritoneal metastasis group (no PM group) based on baseline imaging evaluated by RECIST ver. 1.1 criteria and amount of ascites. OS, progression-free survival, and overall response rate were compared between two arms in each group. Results This study included 240 and 243 patients in the w-nab-PTX and w-sb-PTX arms, respectively. In the PM group, the w-nab-PTX arm (n = 88) had longer OS than the w-sb-PTX arm (n = 103), and median survival time (MST) of 9.9 and 8.7 months [hazard ratio (HR) 0.63; 95% CI 0.45-0.88; P = 0.0060], respectively. In the no PM group, the w-nab-PTX arm (n = 140) had shorter OS than the w-sb-PTX arm (n = 152), and MST of 11.6 and 15.7 months (HR 1.40; 95% CI 1.06-1.86; P = 0.0180), respectively. After adjusting for prognostic factors, the HR for OS in the w-nab-PTX arm versus the w-sb-PTX arm was 0.59 (95% CI 0.42-0.83; P = 0.0023; PM group) and 1.34 (95% CI 1.01-1.78; P = 0.0414; no PM group), with significant interaction between treatment efficacy and presence of peritoneal metastasis (P = 0.0003). Conclusions The presence of apparent peritoneal metastasis might be a predictive factor for selecting w-nab-PTX for pretreated AGC patients. Trial registration number JapicCTI-132059.

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“…Due to its nature, the peritoneum is poorly reached by systemic chemotherapy due to the plasma-peritoneal barrier [ 2 3 4 5 ]. For these reasons intraperitoneal chemotherapy was introduced with promising results: the administration of drug directly into the peritoneal cavity allows an effective dose delivered to the tumor site without reaching plasma toxicity levels [ 4 6 7 8 ]. Moreover, chemotherapeutics could be delivered associated with hyperthermia (hyperthermic intraperitoneal chemotherapy [HIPEC]) increasing the effect of the drug with the heat [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on relapse pattern in primary epithelial ovarian cancer: a propensity score based case-control study

et al. 2018

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ObjectiveHyperthermic intraperitoneal chemotherapy (HIPEC) has been proposed as a treatment in ovarian cancer. A recently published RCT demonstrated that HIPEC prolongs disease-free survival (DFS) and overall survival (OS) in ovarian cancer. The aim of the study was to investigate oncologic results of cytoreductive surgery+HIPEC compared with cytoreductive surgery alone in advanced primary ovarian cancer with a particular attention to the pattern of recurrence.MethodsThis is a retrospective case control study with a propensity score (PS) matching of the patients. All the patients treated for primary advanced ovarian cancer who underwent interval surgery with or without HIPEC were collected; a PS was calculated in order to match cases to controls.ResultsAmong 77 eligible patients 56 patients were included in the study. Preoperative patients' characteristics were homogeneous. No difference in morbidity and mortality after surgery were recorded. DFS was not different among the 2 groups (13.2 vs. 13.9 months, p=0.454) but OS was better in patients treated with HIPEC with no median reached vs. 35.5 months (p=0.048). Patients treated with cytoreductive surgery alone were more likely to have a peritoneal recurrence (43% vs. 14%).ConclusionHIPEC seems to affect the relapse pattern with lesser peritoneal recurrence. This difference in relapse pattern seems to affect the OS with better results in patients treated with HIPEC. Further studies are needed to confirm these findings.

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High Penetration of Paclitaxel in Abdominal Wall of Rabbits after Hyperthermic Intraperitoneal Administration of Nab-Paclitaxel Compared to Standard Paclitaxel Formulation

Abstract: Our results show that nab-paclitaxel penetrates into the abdominal wall better than CRE-paclitaxel, in terms of effective penetration and peritoneal tissue concentration.

Cited by 23 publications

References 39 publications

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis – a phase I first-in-human study

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis – a phase I first-in-human study

Peritoneal metastasis as a predictive factor for nab-paclitaxel in patients with pretreated advanced gastric cancer: an exploratory analysis of the phase III ABSOLUTE trial

Effect of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on relapse pattern in primary epithelial ovarian cancer: a propensity score based case-control study

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