Cytoreductive Surgery and Intraoperative Hyperthermic Intraperitoneal Chemotherapy with Paclitaxel: A Clinical and Pharmacokinetic Study

Bree, Eelco de; Rosing, Hilde; Filis, D.; Romanos, John; Melisssourgaki, Maria; Daskalakis, Markos; Pilatou, M.; Sanidas, Elias; Taflampas, Panagiotis; Kalbakis, K.; Beijnen, Jos H.; Tsiftsis, Dimitris D.

doi:10.1245/s10434-007-9792-y

Cited by 64 publications

(39 citation statements)

References 48 publications

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“…However, rats treated with the nanosuspension recovered faster compared to the group treated with Taxol ® as they already regained their initial body weight 5 days after HIPEC treatment, highlighting the advantage of using the noncytotoxic Pluronic F127 ® . Based on the body surface area, the MTD corresponded to a dose of 960 mg/m 2 , which is much higher compared to the dose administered to humans (175 mg/m 2 ) during HIPEC (20). This underlines one of the opportunities of HIPEC: the possibility to use higher doses, resulting in higher local concentrations which are maintained for a longer time in the abdominal cavity and which have a higher direct cytotoxic effect (21).…”

Section: Nanocrystalline Ptx For Hipec Treatmentmentioning

confidence: 97%

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

et al. 2012

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Purpose: To develop a nanocrystalline paclitaxel formulation with a high paclitaxel-to-stabilizer ratio which can be used for hyperthermic intraperitoneal chemotherapy (HIPEC).Methods: Paclitaxel (PTX) nanocrystals were prepared via wet milling using Pluronic F127 ® as stabilizer. The suitability of paclitaxel nanosuspensions for HIPEC treatment was evaluated by analyzing the cytotoxicity of both stabilizer and formulation, and by determining the maximum tolerated dose (MTD) and bioavailability. The effect on tumor growth was evaluated by magnetic resonance imaging (MRI) at day 7 and 14 after HIPEC treatment in rats with peritoneal carcinomatosis of ovarian origin.Results: Monodisperse nanosuspensions (±400 nm) were developed using Pluronic F127 ® as single additive. The cytotoxicity and MTD of this nanocrystalline formulation was similar compared to Taxol ® , while its bioavailability was higher. MRI data after HIPEC treatment with a PTX nanocrystalline suspension showed a significant reduction of tumor volume compared to the nontreated group. Although no significant differences on tumor volume were observed between Taxol ® and the nanosuspension, the rats treated with the nanosuspension recovered faster following the HIPEC procedure.Conclusion: Nanosuspensions with a high paclitaxel-to-stabilizer ratio are of interest for the treatment of peritoneal carcinomatosis of ovarian origin via HIPEC.

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Section: Nanocrystalline Ptx For Hipec Treatmentmentioning

confidence: 97%

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

et al. 2012

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“…Even in platinum-resistant ovarian cancer, both drugs appear to be active agents. Paclitaxel seems to be a fascinating drug for intraperitoneal chemotherapy because of its highly favourable pharmacokinetic profile (peritoneal to plasma AUC ratio: 550-2,300) due to its large molecular weight that delays absorption from the abdominal cavity [97][98][99]. As response to taxanes appears to be dose dependent for systemic chemotherapy, increased activity is to be expected during intraperitoneal chemotherapy [4].…”

Section: Paclitaxelmentioning

confidence: 99%

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Bree

Michelakis

Stamatiou

et al. 2017

Pleura and Peritoneum

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Intraperitoneal chemotherapy is associated with a significant pharmacokinetic and pharmacodynamic benefit and can, alone or in combination with systemic chemotherapy (bidirectional chemotherapy), be used for treating primary and secondary peritoneal surface malignancies. Due to the peritoneal-plasma barrier, high intraperitoneal drug concentration can be achieved by intraperitoneal chemotherapy, whereas systemic concentration remains low. Bidirectional chemotherapy may provide in addition adequate drug concentrations from the side of the subperitoneal space to the peritoneal tumour nodules. Major pharmacological problems of intraperitoneal chemotherapy are limited tissue penetration and poor homogeneity of drug distribution to the entire seroperitoneal surface. Significant pharmacological determinants of intraperitoneal chemotherapy are choice of drug, drug dosage, solution volume, carrier solution, intra-abdominal pressure, temperature, duration, mode of administration, extent of peritonectomy and interindividual variability. Drugs most commonly applied for intraperitoneal chemotherapy include mitomycin C, cisplatin, carboplatin, oxaliplatin, irinotecan, 5-fluoruracil, gemcitabine, paclitaxel, docetaxel, doxorubicin, premetrexed and melphalan. The drugs and their doses that are used vary widely among centres. While the adequate drug choice for intraperitoneal and bidirectional chemotherapy is essential, randomized clinical trials to determine the most optimal drug or drug combination are lacking, and only eight retrospective comparative clinical studies are available. Further clinical pharmacological studies are required to determine the most effective drug regimen for intraperitoneal and bidirectional chemotherapy in various indications. In the future, reliable drug sensitivity testing and genetic profiling of peritoneal metastases will be needed for enabling patient-specific therapy.

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“…Peritoneal fluid and venous blood samples were collected immediately after the oxaliplatin administration and then every 10 min until the end of the peritoneal perfusion. Additional venous blood samples were drawn at 0.25, 0.5, 1, 1.5, 2, 2.5, 3,4,6,8,12,16,20,24, and 28 h after the end of the peritoneal perfusion. All samples were collected in S-monovette® tubes, centrifuged at 3,500 rpm for 10 min and were stored at −80°C until analysis.…”

Section: Hyperthermic Intraperitonealmentioning

confidence: 99%

“…Consequently, large hydrophilic compounds with limited permeability across an intact peritoneal membrane have been preferred to small lipophilic compounds (12). In this context, cisplatin (13), mytomicin C (14), carboplatin (15), paclitaxel (16), irinotecan (17), and oxaliplatin (18) have been used as chemotherapy agents in HIPEC because their cytotoxic activity is enhanced with hyperthermia. Although comparative studies across these drugs have not been performed to date, the results obtained with oxaliplatin are encouraging.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Analysis of Hyperthermic Intraperitoneal Oxaliplatin-Induced Neutropenia in Subjects with Peritoneal Carcinomatosis

Valenzuela

Nalda-Molina

Bretcha-Boix

et al. 2011

AAPS J

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Abstract. The objective of this study was to characterize the pharmacokinetics and the time course of the neutropenia-induced by hyperthermic intraperitoneal oxaliplatin (HIO) after cytoreductive surgery in cancer patients with peritoneal carcinomatosis. Data from 30 patients who received 360 mg/m 2 of HIO following cytoreductive surgery were used for pharmacokinetic-pharmacodynamic (PK/PD) analysis. The oxaliplatin plasma concentrations were characterized by an open two-compartment pharmacokinetic model after first-order absorption from peritoneum to plasma. An oxaliplatin-sensitive progenitor cell compartment was used to describe the absolute neutrophil counts in blood. The reduction of the proliferation rate of the progenitor cells was modeled by a linear function of the oxaliplatin plasma concentrations. The typical values of oxaliplatin absorption and terminal half-lives were estimated to be 2.2 and 40 h, with moderate interindividual variability. Oxaliplatin reduced the proliferation rate of the progenitor cells by 18.2% per mg/L. No patient's covariates were related to oxaliplatin PK/PD parameters. Bootstrap and visual predictive check evidenced the model was deemed appropriate to describe oxaliplatin pharmacokinetics and the incidence and severity of neutropenia. A peritoneum oxaliplatin exposure of 65 and 120 mg·L/h was associated with a 20% and 33% incidence of neutropenia grade 4. The time course of neutropenia following HIO administration was well described by the semiphysiological PK/PD model. The maximum tolerated peritoneum oxaliplatin exposure is 120 mg L/h and higher exposures should be avoided in future studies. We suggest the prophylactic use of granulocyte colony stimulating factor for patients treated with HIO exposure higher than 65 mg L/h.

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Cytoreductive Surgery and Intraoperative Hyperthermic Intraperitoneal Chemotherapy with Paclitaxel: A Clinical and Pharmacokinetic Study

Cited by 64 publications

References 48 publications

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Pharmacokinetic and Pharmacodynamic Analysis of Hyperthermic Intraperitoneal Oxaliplatin-Induced Neutropenia in Subjects with Peritoneal Carcinomatosis

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