Pre-clinical study of the epinephrine–cisplatin association for the treatment of intraperitoneal carcinomatosis

Favoulet, P; Magnin, Guy; Guilland, Jean-Claude; Beltramo, Jean-Luc; Osmak, Liliana; Beaugerie, Laurent; Rat, Patrick; Douvier, S.; Duvillard, C.; Chauffert, Bruno

doi:10.1053/ejso.2000.1028

Cited by 19 publications

(12 citation statements)

References 11 publications

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“…Besides the drug characteristics and pharmacokinetic variables, their penetration depth is determined by factors such as tumour nodule size, cell density, extracellular matrix, vascularity, interstitial fluid pressure and binding [18,19]. Various mathematical models have been proposed which can provide unique insights into the different transport barriers that occur during intraperitoneal chemotherapy [17,[19][20][21].…”

Section: Pharmacodynamic Aspects Of Intraperitoneal Chemotherapymentioning

confidence: 99%

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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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Section: Pharmacodynamic Aspects Of Intraperitoneal Chemotherapymentioning

confidence: 99%

“…The characteristics that are most important for their application in intraperitoneal chemotherapy are summarized in Table 3 [4,20,66,67].…”

Section: Drugs Commonly Administered In Intraperitoneal Chemotherapymentioning

confidence: 99%

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Bree

Michelakis

Stamatiou

et al. 2017

Pleura and Peritoneum

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“…This reflects the pharmacological advantage of IPC to obtain high local drug concentrations in the abdominal wall, peritoneum and muscle lining, all of which are possibly infiltrated by malignant cells in peritoneal carcinomatosis. In previous studies we used a higher concentration of adrenaline (5 or 10 mg/L) [18,19]. In the present study it was reduced according to a recent phase I clinical trial, which established the safety of 2 mg/l of adrenaline, whereas 3 mg/l induced cardiovascular collateral effects (tachycardia, arterial hypertension or electric signs of cardiac ischemia) [21].…”

Section: Discussionmentioning

confidence: 99%

“…In previous papers, we reported that intraperitoneal adrenaline increased platinum uptake in rat peritoneal tumor nodules by a factor of 2 to 3 [17-19]. Adrenaline acts through vasoconstriction by limiting drug wash out from the peritoneal cavity.…”

Section: Introductionmentioning

confidence: 99%

Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murin model of peritoneal carcinomatosis

Facy

Radais

Ladoire

et al. 2011

J Exp Clin Cancer Res

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BackgroundThe best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis.MethodsFour groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured in vivo (tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and in vitro (cytotoxicity on human ovarian cancer cells).ResultsIn vitro, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. In vivo, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia.ConclusionAdrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.

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“…Both intravenous and intraperitoneal administration of vasoactive molecules in combination with chemotherapeutic drugs has been explored [36,62,63] . A preclinical study of the use of an intraperitoneal epinephrine plus intraperitoneal cisplatin in a rat model with PC, showed a direct correlation between the intraperitoneal epinephrine concentration and cisplatin accumulation in rat peritoneal tumor nodules [64] . Recently, Molucon-Chabrot et al [65] demonstrated for the first time the safe use of intraperitoneal epinephrine with intraperitoneal cisplatin in 18 patients with advanced peritoneal carcinomatosis.…”

Section: Vasoactive Agentsmentioning

confidence: 99%