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

Élias, Dominique; Matsuhisa, Tadashi; Sidéris, Lucas; Liberale, Gabriel; Drouard-Troalen, L.; Raynard, Bruno; Pocard, Marc; Puizillou, J. M.; Billard, V.; Bourget, Philippe; Ducreux, Michel

doi:10.1093/annonc/mdh398

Cited by 116 publications

(61 citation statements)

References 24 publications

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“…Moreover, 5 out of 8 patients who have received irinotecan-based second-line chemotherapy seemed to benefit from this treatment, as suggested previously by two case reports [19, 20]. This benefit was evident in 1 patient, in whom biological complete response made it possible to perform surgical peritoneal cytoreduction and hyperthermic intraperitoneal chemotherapy, as proposed for selected patients with peritoneal carcinomatosis of colorectal origin [21]. …”

Section: Discussionmentioning

confidence: 71%

Combination Chemotherapy in Advanced Small Bowel Adenocarcinoma

Locher¹,

Malka²,

Boige³

et al. 2005

Oncology

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Objective: To assess the efficacy of 5-fluorouracil (5-FU) and either platinum compounds or irinotecan in patients with advanced small bowel adenocarcinoma (SBA), for whom data on the efficacy of chemotherapy are scarce. Methods: We reviewed data on all patients with advanced SBA who received chemotherapy over a 9-year period at our institution. Results: Twenty patients with advanced SBA received a median of 6 cycles (range 2–15) of chemotherapy with 5-FU and either cisplatin (n = 15), carboplatin (n = 2), or oxaliplatin (n = 3). The overall response rate was 21%, and median progression-free and overall survival 8 and 14 months, respectively. Toxicity was moderate. Second-line chemotherapy with 5-FU and irinotecan resulted in disease stabilization in 4 (50%) of 8 patients (median progression-free survival: 5 months), and in a biological complete response in another patient with nonmeasurable peritoneal carcinomatosis, allowing surgical cytoreduction surgery and hyperthermic intraperitoneal chemotherapy. No tumor response or disease stabilization was seen among the patients who received protracted venous infusion of 5-FU (n = 4) or infusional 5-FU and cisplatin (n = 1) as second-line chemotherapy. Conclusion: Chemotherapy with 5-FU and platinum compounds seems effective and well-tolerated in patients with advanced SBA. 5-FU-irinotecan combination chemotherapy deserves further investigation in the first-line setting.

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Section: Discussionmentioning

confidence: 71%

Combination Chemotherapy in Advanced Small Bowel Adenocarcinoma

Locher¹,

Malka²,

Boige³

et al. 2005

Oncology

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“…Irinotecan is usually metabolized to its active form SN-38 by carboxylesterase in the liver. However, SN-38 has been demonstrated in the peritoneal fluid immediately after the initiation of the HIPEC procedure with irinotecan, proposing the existence of carboxylesterase in the peritoneal cavity of patients suffering from peritoneal metastases [83]. The mean peritoneal to plasma drug exposure ratio was 15 for irinotecan and 4 for its active form, SN-38 in a mouse model, respectively [84].…”

Section: Oxaliplatinmentioning

confidence: 99%

“…The mean peritoneal to plasma drug exposure ratio was 15 for irinotecan and 4 for its active form, SN-38 in a mouse model, respectively [84]. More importantly, the irinotecan concentration in the tumour region, bathed in the perfusate, was 16 to 23 times higher than that in non-bathed muscle tissue in a clinical study [83]. Controversy regarding the synergism between irinotecan and the application of heat exists in published experimental studies [4].…”

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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“…Thus, it appears natural to use a regional treatment in PM [2731] . Sugarbaker's research was regarded mistrustfully, and 25 years had to pass before the "European contributions to the Sugarbaker protocol" [32] appeared: One multicenter retrospective study [33] , two randomized prospective phase Ⅲ studies [34,35] and the use of oxaliplatin and irinotecan as new cytostatic drugs in the protocols for intraperitoneal chemotherapy [36,37] . Sugarbaker also has the merit of being the first to have described and implemented the surgical procedures associated with regional chemotherapy, generically named "Peritonectomy" [38] .…”

Section: Multimodal Treatment -Methods and Foundation-laying (1980-2000)mentioning

confidence: 99%

Multimodality treatment strategies have changed prognosis of peritoneal metastases

Lungoci

Mironiuc

Muntean

et al. 2016

WJGO

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For a long time, treatment of peritoneal metastases (PM) was mostly palliative and thus, this status was link with "terminal status/despair". The current multimodal treatment strategy, consisting of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), has been strenuously achieved over time, but seems to be the best treatment option for PM patients. As we reviewed the literature data, we could emphasize some milestones and also, controversies in the history of proposed multimodal treatment and thus, outline the philosophy of this approach, which seems to be an unusual one indeed. Initially marked by nihilism and fear, but benefiting from a remarkable joint effort of human and material resources (multi-center and -institutional research), over a period of 30 years, CRS and HIPEC found their place in the treatment of PM. The next 4 years were dedicated to the refinement of the multimodal treatment, by launching research pathways. In selected patients, with requires training, it demonstrated a significant survival results (similar to the Hepatic Metastases treatment), with acceptable risks and costs. The main debates regarding CRS and HIPEC treatment were based on the oncologists' perspective and the small number of randomized clinical trials. It is important to statement the PM patient has the right to be informed of the existence of CRS and HIPEC, as a real treatment resource, the decision being made by multidisciplinary teams. Core tip: The multimodal treatment of peritoneal metastases (PM), involving cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, has been strenuously achieved over time, but seems to be the best treatment option, for selected cases. This paper addresses data about the multimodal treatment strategy, focused to patient's survival, the key indicator for assessing results, in the case of PM. Also, it were highlighted the treatment key aspects and the controversies, high in the 35 years of treatment implementing. By understanding the philosophy of multimodal treatment, physicians will be able to offer an alternative to the routine systemic chemotherapy.Lungoci C, Mironiuc AI, Muntean V, Oniu T, Leebmann H, Mayr M, Piso P. Multimodality treatment strategies have changed prognosis of peritoneal metastases.

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

Abstract: Intraperitoneal heated oxaliplatin (460 mg/m(2)) plus irinotecan (400 mg/m(2)) presented an advantageous PK profile and was tolerated by patients, despite a high hematological toxicity rate.

Cited by 116 publications

References 24 publications

Combination Chemotherapy in Advanced Small Bowel Adenocarcinoma

Combination Chemotherapy in Advanced Small Bowel Adenocarcinoma

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Multimodality treatment strategies have changed prognosis of peritoneal metastases

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