High Pressure Enhances the Effect of Hyperthermia in Intraperitoneal Chemotherapy With Oxaliplatin

Facy, Olivier; Samman, Sophie Al; Magnin, Guy; Ghiringhelli, François; Ladoire, Sylvain; Chauffert, Bruno; Rat, Patrick; Ortega‐Deballon, Pablo

doi:10.1097/sla.0b013e3182582b38

Cited by 74 publications

(43 citation statements)

References 27 publications

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“…Several phase III trials have been launched to define the life-saving impact of HIPEC in patients with advanced abdominopelvic malignancies (Ceelen and Flessner, 2010); meanwhile, the pharmacological aspects of intraperitoneal chemotherapy remain the matter of preclinical and clinical studies (Shah et al, 2009(Shah et al, , 2011Chambers et al, 2012;Facy et al, 2012). We characterized the pharmacokinetics of PLD administered by intraoperative HIPEC to women with ovarian carcinomatosis.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Pegylated Liposomal Doxorubicin Administered by Intraoperative Hyperthermic Intraperitoneal Chemotherapy to Patients with Advanced Ovarian Cancer and Peritoneal Carcinomatosis

et al. 2012

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ABSTRACT:The pharmacokinetics of pegylated liposomal doxorubicin (PLD) were investigated in 17 women undergoing intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced ovarian cancer and peritoneal carcinomatosis. HIPEC was performed immediately after completing debulking surgery, which included a number of peritonectomy procedures. PLD was injected and allowed to equilibrate in peritoneal cavity filled with 4 liters of physiological solution and stabilized at 42°C; next, the outflow line was opened and perfusion proceeded for 1 h. PLD was stable in peritoneal perfusate and plasma. During HIPEC, PLD peritoneal perfusate/plasma gradients averaged ϳ600 or >1000 for peak concentration or area under the curve. After HIPEC, PLD plasma levels remained stable or decreased. Biopsy samples of residual normal peritoneum or ovarian carcinomatosis were collected at the end of HIPEC and were shown to contain free doxorubicin. Correlating PLD decrements in peritoneal perfusate with plasma exposure to PLD or peritoneal deposition of free doxorubicin showed that the former occurred during preperfusional equilibration of PLD in peritoneal cavity, whereas the latter occurred during 1 h of perfusion. Plasma exposure to PLD correlated negatively with the number of peritonectomy procedures performed during surgery, whereas peritoneal deposition of free doxorubicin correlated positively. Taken together, these results show that PLD administered by intraoperative HIPEC undergoes limited systemic diffusion and releases active free doxorubicin in peritoneum exposed to ovarian carcinomatosis. PLD pharmacokinetics seem to be influenced by peritonectomy procedures.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Pegylated Liposomal Doxorubicin Administered by Intraoperative Hyperthermic Intraperitoneal Chemotherapy to Patients with Advanced Ovarian Cancer and Peritoneal Carcinomatosis

et al. 2012

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“…In various animal models [52][53][54], a higher intraabdominal pressure resulted in increased drug concentrations in peritoneum, tissues and tumour nodules, an increased penetration depth of the drug into the tumour nodules and decreased intraperitoneal vs. systemic AUC ratio. In a pig model, laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC), associated with an increased intra-abdominal pressure, resulted in higher drug absorption from the abdominal cavity to the systemic compartment when compared with the open abdomen, coliseum technique [55].…”

Section: Intra-abdominal Pressurementioning

confidence: 99%

“…Moreover, experimental data indicate that hyperthermia may enhance the penetration depth of intraperitoneally delivered chemotherapeutic drugs into tissues and tumour nodules, without changing the pharmacokinetic profile. The thermal enhancement of the drugs' activity and penetration depth is often already observed at temperatures above 39-40°C [14,54,[61][62][63]. Regardless of these theoretical advantages, to our knowledge, there is no high-level evidence (i. e. a comparative clinical study) that HIPEC is superior to normothermic intraperitoneal chemotherapy.…”

Section: Hyperthermiamentioning

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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“…1e4 PIPAC combines the benefits of intraperitoneal administration (increased intra-tumoral concentrations, 5,6 low systemic toxicity 4,7 ), pressurized vaporization (homogenous distribution, 2 deep penetration 4,5,8 ) and minimal-invasive approach (repetitive application possible, low morbidity, better quality of life 9e13 ). Most scientific studies on PIPAC were published by the pioneer team in Germany which elaborated also safety rules in order to minimize occupational health risks.…”

Section: Introductionmentioning

confidence: 99%

Pressurized IntraPeritoneal Aerosol Chemotherapy – Practical aspects

Hübner

Grass

Farinha

et al. 2017

European Journal of Surgical Oncology (EJSO)

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High Pressure Enhances the Effect of Hyperthermia in Intraperitoneal Chemotherapy With Oxaliplatin

Abstract: Open high-pressure HIPEC with oxaliplatin is feasible in the pig. Hyperthermia enhances diffusion in the visceral peritoneum, whereas high pressure is effective in the visceral and parietal peritoneum. The combination of the two achieves the highest tissue concentrations of oxaliplatin.

Cited by 74 publications

References 27 publications

Pharmacokinetics of Pegylated Liposomal Doxorubicin Administered by Intraoperative Hyperthermic Intraperitoneal Chemotherapy to Patients with Advanced Ovarian Cancer and Peritoneal Carcinomatosis

Pharmacokinetics of Pegylated Liposomal Doxorubicin Administered by Intraoperative Hyperthermic Intraperitoneal Chemotherapy to Patients with Advanced Ovarian Cancer and Peritoneal Carcinomatosis

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Pressurized IntraPeritoneal Aerosol Chemotherapy – Practical aspects

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