Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution

Élias, Dominique; Bonnay, M; Puizillou, J. M.; Antoun, Sami; Demirdjian, Sylvie; Otmany, A. El; Pignon, Jean-Pierre; Drouard-Troalen, L.; Ouellet, Jean-François; Ducreux, Michel

doi:10.1093/annonc/mdf019

Cited by 314 publications

(171 citation statements)

References 15 publications

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“…Interestingly, this difference in the platelet and neutrophil toxicity was only observed in patients who had undergone a splenectomy. However, this study had used a much longer duration of oxaliplatin HIPEC (2 hours) compared to the most commonly used oxaliplatin based HIPEC protocol (30 min chemoperfusion), described by Elias et al [37]. In fact, in a French multi-centric study [38] evaluating the role of HIPEC in GI origin peritoneal metastases, the incidence of hematological toxicity from oxaliplatin or MMC based HIPEC regimens was not different.…”

Section: Hematological Complicationsmentioning

confidence: 91%

Complications of Cytoreductive Surgery and HIPEC in the Treatment of Peritoneal Metastases

Mehta

Gelli

Agarwal

et al. 2016

Indian J Surg Oncol

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The combined treatment concept of cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown to be an efficient therapeutic option for selected patients with primary and secondary peritoneal carcinomatosis (PC). This strategy represents the standard of care for diseases like pseudomyxoma peritonei and peritoneal mesothelioma, and offers the best long-term results for PC from colorectal cancer. Despite these results, skepticism exists regarding this therapeutic approach partly because of its perceived high toxicity. In this article, we review the current evidence on complications that can occur after CRS and HIPEC and the risk factors associated with increased incidence of morbidity and mortality.

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Section: Hematological Complicationsmentioning

confidence: 91%

Complications of Cytoreductive Surgery and HIPEC in the Treatment of Peritoneal Metastases

Mehta

Gelli

Agarwal

et al. 2016

Indian J Surg Oncol

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“…The low peritoneal AUC (peritoneal to plasma AUC ratio: 16) is counterbalanced by the rapid drug uptake by tumour cells until an estimated depth of 1-2 mm, while hyperthermia enhances the tissue concentration [4,76,77]. Moreover, its activity during HIPEC is enhanced by concurrent administration of the combination of 5-fluorouracil (400 mg/m 2 ) and leucovorin (20 mg/m 2 ) intravenously [25].…”

Section: Oxaliplatinmentioning

confidence: 99%

“…Moreover, its activity during HIPEC is enhanced by concurrent administration of the combination of 5-fluorouracil (400 mg/m 2 ) and leucovorin (20 mg/m 2 ) intravenously [25]. This bidirectional intraoperative strategy has been innovated by the group of Elias [25,32,76]. Intraperitoneal chemotherapy with oxaliplatin is generally well tolerated, but the high dose of 460 mg/m 2 for 30 min was related to a significant risk of postoperative haemorrhage [78].…”

Section: Oxaliplatinmentioning

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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“…All these characteristics had already been studied for oxaliplatin (Table 3) which is featured in many lines of systemic chemotherapy in colorectal cancer [1] and which also is in many specialized centers the elective drug for HIPEC in PC of colorectal origin [42,43]. The suboptimal parameter for this molecule is the AUC peritoneal-plasma ratio, calculated at 3.5-5, which compares unfavorably with other drugs such as cisplatin [12][13][14][15][16][17][18][19][20][21] or paclitaxel (1000) ( Table 4).…”

Section: Drug Selectionmentioning

confidence: 99%

Preoperative intraperitoneal oxaliplatin for unresectable peritoneal carcinomatosis of colorectal origin: a pilot study

Sgarbură

Samalin

Carrère

et al. 2016

Pleura and Peritoneum

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Background: Peritoneal carcinomatosis in colorectal cancer is an advanced stage of the disease where improved survival can be attained whenever the resection associated with hyperthermic intreperitoneal chemotherapy is possible. In unresectable cases, systemic chemotherapy is administered to obtain conversion to resectability but results have not yet been clearly evaluated. Local chemotherapy in this setting has been proven useful in several similar situations. The aim of the present pilot study was to evaluate the feasibility of preoperative intraperitoneal chemotherapy with oxaliplatin in these patients. Methods: Six patients with unresectable peritoneal disease of colorectal origin were included in the study. An intraperitoneal implantable chamber catheter was inserted during the laparotomy that evaluated the extent of the peritoneal disease (peritoneal

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Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution

Cited by 314 publications

References 15 publications

Complications of Cytoreductive Surgery and HIPEC in the Treatment of Peritoneal Metastases

Complications of Cytoreductive Surgery and HIPEC in the Treatment of Peritoneal Metastases

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Preoperative intraperitoneal oxaliplatin for unresectable peritoneal carcinomatosis of colorectal origin: a pilot study

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