The Treatment of Peritoneal Carcinomatosis of Colorectal Cancer with Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Peroperative Chemotherapy (HIPEC) with Oxaliplatin: A Belgian Multicentre Prospective Phase II Clinical Study

Hompes, Daphne; D’Hoore, André; Cutsem, Éric Van; Fieuws, Steffen; Ceelen, Wim; Peeters, Marc; Speeten, Kurt Van der; Bertrand, C.; Legendre, Hugues; Kerger, Joseph

doi:10.1245/s10434-012-2264-z

Cited by 98 publications

(76 citation statements)

References 42 publications

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“…In this context, intraperitoneal (IP) administration of chemotherapeutics has shown to be superior over the intravenous route [11,12], particularly due to the ability to maintain high concentrations of cytotoxic agents in the peritoneal cavity [13]. Also, promising data have resulted from clinical trials evaluating hyperthermic intraperitoneal chemoperfusion (HIPEC) immediately after cytoreductive surgery [14,15]. HIPEC involves flushing the peritoneal cavity with chemotherapeutic agents at an elevated temperature of 41-42°C.…”

Section: Introductionmentioning

confidence: 99%

Colloidal stability of nano-sized particles in the peritoneal fluid: Towards optimizing drug delivery systems for intraperitoneal therapy

et al. 2014

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Intraperitoneal (IP) administration of nano-sized delivery vehicles containing small interfering RNA (siRNA) is recently gaining attention as an alternative route for the efficient treatment of peritoneal carcinomatosis. The colloidal stability of nanomatter following IP administration has, however, not been thoroughly investigated yet. Here, enabled by advanced microscopy methods such as Single Particle Tracking (SPT) and Fluorescence Correlation Spectroscopy (FCS), we follow the aggregation and cargo release of nano-scaled systems directly in peritoneal fluids from healthy mice and ascites fluid from a patient diagnosed with peritoneal carcinomatosis. The colloidal stability in the peritoneal fluids was systematically studied in function of the charge (positive or negative) and Poly-Ethylene Glycol (PEG) degree of liposomes and polystyrene nanoparticles, and compared to human serum. Our data demonstrate strong aggregation of cationic and anionic nanoparticles in the peritoneal fluids, while only slight aggregation was observed for the PEGylated ones. PEGylated liposomes, however, lead to a fast and premature release of siRNA cargo in the peritoneal fluids. Based on our observations, we reflect on how to tailor improved delivery systems for IP therapy.

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Section: Introductionmentioning

confidence: 99%

Colloidal stability of nano-sized particles in the peritoneal fluid: Towards optimizing drug delivery systems for intraperitoneal therapy

et al. 2014

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“…Furthermore, metastasis or recurrence occurs in a large number of patients following surgical resection, affecting the prognosis of the patients. Therefore, the five-year survival rate is low (64%), posing a serious threat to patient health (5,6).…”

Section: Introductionmentioning

confidence: 99%

Expression and clinical significance of Sirt1 in colorectal cancer

Jiang

Pan

et al. 2015

Oncology Letters

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Abstract. The objective of the present study was to examine the expression of Silent information regulator 1 (Sirt1) in colorectal cancer and peritumoral normal mucosa tissue, and therefore analyze the role and molecular mechanism of Sirt1 in the pathogenesis of colorectal cancer. Colorectal cancer tissue specimens were employed as the experimental group, and adjacent normal mucosa tissues >5 cm from tumor lesions were used as the control group. The expression of Sirt1 was detected by the immunohistochemical streptavidin peroxidase detection method in paraffin-embedded sections, whilst Sirt1 protein expression was examined by western blot analysis in the fresh tissues. Sirt1 protein was primarily expressed in the nuclei of the tumor cells, and positive staining was brownish-yellow in color. The relative expression quantities of Sirt1 in the peritumoral normal rectal mucosa and rectal carcinoma were 1.15 and 2.62, and the differences between the two groups were statistically significant (P<0.05). The expression level of Sirt1 in colorectal carcinoma was significantly associated with the depth of tumor invasion, differentiation and tumor size (P<0.05). Sirt1 expression was also found to be associated with tumor tissue type, lymph node metastasis, Duke's stage and patient age. These characteristics combined may therefore be used as markers for the early diagnosis of colorectal cancer pathogenesis. IntroductionColorectal cancer occurs in the colorectal mucosa and colonic glands and is one of the most common types of malignant tumor of the digestive system (1,2). The worldwide incidence and mortality rates of colorectal cancer increased significantly between 2009 and 2013; in 2013, a total of 142,820 new cases were diagnosed and 50,830 mortalities occurred as a result of colorectal cancer (3). Thus, this malignancy presents a serious threat to human health (1,2). Clinical and pathological data of patients with colorectal cancer in China have demonstrated the following pathogenic characteristics: The number of patients in cities is higher than that in the countryside, indicating a clear urbanization trend; and patients <30 years of age account for >10% of the total number of patients, demonstrating a clear trend towards older age (4). Surgical resection is currently the main method used for the treatment of colorectal cancer. However, as significant symptoms are often not present in the early stages of the disease, patients are frequently diagnosed in the later stages; by this time, the optimal period for surgery has passed. Furthermore, metastasis or recurrence occurs in a large number of patients following surgical resection, affecting the prognosis of the patients. Therefore, the five-year survival rate is low (64%), posing a serious threat to patient health (5,6).The occurrence and pathogenesis of colorectal cancer is a complex, multistep process, regulated by a number of different genes (1). A total of 25% of patients with colorectal cancer have a genetic history, which is associated with familial adenomatous pol...

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“…The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal oxaliplatin (HIO) is a promising strategy for PC treatment (2) since retrospective and prospective analyses, including phase II and phase III clinical trials, as well as meta-analysis, have evidenced its survival benefit, relative to standard palliative surgery and/or chemotherapy (SPSC), in patients with resectable PC of colorectal origin (3,4). The efficacy of this innovative treatment has also been reported in phase II studies in ovarian cancer (5,6) and in phase III studies in gastric cancer (7,8).…”

Section: Introductionmentioning

confidence: 99%

Platelet Dynamics in Peritoneal Carcinomatosis Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Oxaliplatin

Pérez-Ruixo

Valenzuela

Peris

et al. 2015

AAPS J

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Abstract. The aim of the study was to characterize the platelet count (PLT) dynamics in peritoneal carcinomatosis patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal oxaliplatin (HIO). Data from patients treated with CRS alone (N=18) or CRS and HIO (N=62) were used to estimate the baseline platelet count (PLT 0 ), rate constants for platelet maturation (k tr ) and platelet random destruction (k s ), feedback on progenitor cell proliferation (γ), and the drug-specific model parameters (α, β). Plasma oxaliplatin concentrations, C p , reduced the proliferation rate of progenitor cells (k prol ) according to a power function α×C p β . The surgery effect on k prol and k s was explored. The typical values (between subject variability) of the PLT 0 , k tr , k s , γ, α, and β were estimated to be 237×10 9 cells/L (32.9%), 7.09×10 −3 h −1 (47.1%), 8.86×10 −3 h −1 (80.0%), 0.621, 0.88 L/mg (56.9%), and 2.63. Surgery induced a maximal 2.09-fold increase in k prol that was attenuated with a half-life of 8.42 days. Splenectomy decreased k s by 47.5%. Age, sex, body surface area, sex, total proteins, and HIO carrier solution did not impact the model parameters. The model developed suggests that, following CRS and HIO, thrombocytopenia and thrombocytosis were reversible and short-lasting; the severity of the thrombocytopenia and thrombocytosis was inversely correlated, with splenectomized patients having thrombocytopenia of lower severity and thrombocytosis of higher severity; and the HIO dose and treatment duration determine the severity and duration of the thrombocytopenia. Higher HIO dose or longer treatment duration could be used without substantially increasing the risk of major hematological toxicity.

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The Treatment of Peritoneal Carcinomatosis of Colorectal Cancer with Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Peroperative Chemotherapy (HIPEC) with Oxaliplatin: A Belgian Multicentre Prospective Phase II Clinical Study

Abstract: CCRS followed by HIPEC with oxaliplatin for PC from CRC can be implemented with acceptable morbidity. Long-term DFS and OS can be achieved in selected patients.

Cited by 98 publications

References 42 publications

Colloidal stability of nano-sized particles in the peritoneal fluid: Towards optimizing drug delivery systems for intraperitoneal therapy

Colloidal stability of nano-sized particles in the peritoneal fluid: Towards optimizing drug delivery systems for intraperitoneal therapy

Expression and clinical significance of Sirt1 in colorectal cancer

Platelet Dynamics in Peritoneal Carcinomatosis Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Oxaliplatin

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