Intra-operative intra-peritoneal chemotherapy with cisplatin in patients with peritoneal carcinomatosis of ovarian cancer

International audienceBACKGROUND: Intra-peritoneal (i.p.) chemotherapy is an encouraging treatment option for ovarian cancer with peritoneum involvement in addition with intravenous (i.v.) chemotherapy. Intra-operative i.p. chemotherapy is an interesting method of administration by enhancing the diffusion of chemotherapy. This study had assessed the feasibility of intra-operative i.p. chemotherapy in patients with peritoneal carcinoma of ovarian cancer. METHODS: From January 2003 to February 2006, 47 patients with stage III ovarian cancer were treated with standard paclitaxel carboplatin intravenous chemotherapy and debulking surgery with intra-operative i.p. chemotherapy. After optimal cytoreductive surgery, defined by no unresectable residual disease > 1 cm, i.p. chemotherapy was performed during surgery. The peritoneal cavity was filled by 3 litres of isotonic saline pre-heated at 37 degrees and 90 mg of cisplatin. The sequence was repeated twice during 2 hours based on previous published studies which optimized the cisplatin dosage and exposure duration. Optimal diffusion was obtained by stirring by hands during the 2 hours. RESULTS: Median age was 59.6 years. No severe haematological or non-haematological toxicity induced by intra operative i.p. chemotherapy was reported. No patient died due to the complications of surgery or the i.p. chemotherapy. No neurotoxicity occurred, and one patients had renal impairment. CONCLUSION: This study demonstrates the feasibility of intra-operative i.p. chemotherapy with cisplatin after optimal resection of peritoneal tumor nodules. Further randomized trials are planned to investigate the clinical benefit of this therapeutic modality

High-pressure intrapleural chemotherapy: feasibility in the pig model.

International audienceABSTRACT: BACKGROUND: The usual treatments for pleural malignancies are mostly palliative. In contrast, peritoneal malignancies are often treated with a curative intent by cytoreductive surgery and intraperitoneal chemotherapy. As pressure has been shown to increase antitumor efficacy, we applied the concept of high-pressure intracavitary chemotherapy to the pleural space in a swine model. METHODS: Cisplatin and gemcitabine were selected because of their antineoplasic efficacy in vitro in a wide spectrum of cancer cell lines. The pleural cavity of 21 pigs was filled with saline solution; haemodynamic and respiratory parameters were monitored. The pressure was increased to 15-25 cm H2O. This treatment was associated with pneumonectomy in 6 pigs. Five pigs were treated with chemotherapy under pressure. RESULTS: The combination of gemcitabine (100 mg/l) and cisplatin (30 mg/l) was highly cytotoxic in vitro. The maximum tolerated pressure was 20 cm H20, due to haemodynamic failure. Pneumonectomy was not tolerated, either before or after pleural infusion. Five pigs survived intrapleural chemotherapy associating gemcitabine and cisplatin with 20 cm H2O pressure for 60 min. CONCLUSIONS: High-pressure intrapleural chemotherapy is feasible in pigs. Further experiments will establish the pharmacokinetics and determine whether the benefit already shown in the peritoneum is also obtained in the pleura

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

<p>Abstract</p> <p>Background</p> <p>The 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.</p> <p>Methods</p> <p>Four 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 <it>in vivo </it>(tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and <it>in vitro </it>(cytotoxicity on human ovarian cancer cells).</p> <p>Results</p> <p><it>In vitro</it>, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. <it>In vivo</it>, 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.</p> <p>Conclusion</p> <p>Adrenaline 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.</p

Tumor cells convert immature myeloid dendritic cells into TGF-β–secreting cells inducing CD4+CD25+ regulatory T cell proliferation

The mechanisms through which regulatory T cells accumulate in lymphoid organs of tumor-bearing hosts remain elusive. Our experiments indicate that the accumulation of CD4+CD25+ regulatory T cells (T reg cells) expressing FoxP3 and exhibiting immunosuppressive function originates from the proliferation of naturally occurring CD25+ T cells and requires signaling through transforming growth factor (TGF)–β receptor II. During tumor progression, a subset of dendritic cells (DCs) exhibiting a myeloid immature phenotype is recruited to draining lymph nodes. This DC subset selectively promotes the proliferation of T reg cells in a TGF-β–dependent manner in mice and rats. Tumor cells are necessary and sufficient to convert DCs into regulatory cells that secrete bioactive TGF-β and stimulate T reg cell proliferation. In conclusion, tumor expansion can stimulate T reg cells via a specific DC subset

Clinical Study A Reappraisal of Chemotherapy-Induced Liver Injury in Colorectal Liver Metastases before the Era of Antiangiogenics

Background and Aims. Chemotherapy of colorectal liver metastases can induce hepatotoxicity in noncancerous liver. We describe these lesions and assess risk factors and impacts on postresection morbidity and mortality in naive patients to chemotherapy before the era of bevacizumab. Methods. Noncancerous liver tissue lesions were analysed according to tumour, chemotherapy, surgery, and patient characteristics. Results. Fifty patients aged 62 ± 9.3 years were included between 2003 and 2007. Thirty-three (66%) received chemotherapy, with Folfox (58%), Folfiri (21%), LV5FU2 (12%), or Xelox (9%) regimens. Hepatotoxicity consisted of 18 (36%) cases of severe sinusoidal dilatation (SD), 13 (26%) portal fibrosis, 7 (14%) perisinusoidal fibrosis (PSF), 6 (12%) nodular regenerative hyperplasia (NRH), 2 (4%) steatosis &gt;30%, zero steatohepatitis, and 16 (32%) surgical hepatitis. PSF was more frequent after chemotherapy (21% versus 0%, = 0.04), especially LV5FU2 ( = 0.02). SD was associated with oxaliplatin (54.5% versus 23.5%, = 0.05) and low body mass index ( = 0.003). NRH was associated with oxaliplatin ( = 0.03) and extensive resection ( = 0.04). No impact on mortality and morbidity was observed, apart postoperative elevation of bilirubin levels in case of PSF ( = 0.03), longer hospitalization in case of surgical hepatitis ( = 0.03), and greater blood loss in case of portal fibrosis ( = 0.03). Conclusions. Chemotherapy of colorectal liver metastases induces sinusoidal dilatation related to oxaliplatin and perisinusoidal fibrosis related to 5FU, without any impact on postoperative mortality

Evaluation of Proton MR Spectroscopy for the Study of the Tongue Tissue in Healthy Subjects and Patients With Tongue Squamous Cell Carcinoma: Preliminary Findings

PurposeTo noninvasively assess spectroscopic and metabolic profiles of healthy tongue tissue and in an exploratory objective in nontreated and treated patients with tongue squamous cell carcinoma (SCC).MethodsFourteen healthy subjects (HSs), one patient with nontreated tongue SCC (NT-SCC), and two patients with treated tongue SCC (T-SCC) underwent MRI and single-voxel proton magnetic resonance spectroscopy (1H-MRS) evaluations (3 and 1.5T). Multi-echo-times 1H-MRS was performed at the medial superior part (MSP) and the anterior inferior part (AIP) of the tongue in HS, while 1H-MRS voxel was placed at the most aggressive part of the tumor for patients with tongue SCC. 1H-MRS data analysis yielded spectroscopic metabolite ratios quantified to total creatine.ResultsIn HS, compared to MSP and AIP, 1H-MRS spectra revealed higher levels of creatine, a more prominent and well-identified trimethylamine-choline (TMA-Cho) peak. However, larger prominent lipid peaks were better differentiated in the tongue MSP. Compared to HS, patients with NT-SCC exhibited very high levels of lipids and relatively higher values of TMA-Cho peak. Interestingly, patients with T-SCC showed almost nonproliferation activity. However, high lipids levels were measured, although they were relatively lower than lipids levels measured in patients with NT-SCC.ConclusionThe present study demonstrated the potential use of in-vivo1H-MRS to noninvasively assess spectroscopic and metabolic profiles of the healthy tongue tissue in a spatial location-dependent manner. Preliminary results revealed differences between HS and patients with tongue NT-SCC as well as tongue T-SCC, which should be confirmed with more patients. 1H-MRS could be included, in the future, in the arsenal of tools for treatment response evaluation and noninvasive monitoring of patients with tongue SCC

BILAN D'UTILISATION DE L'OXALIPLATINE SUR UNE PERIODE DE DEUX ANS DANS UN SERVICE DE MEDECINE INTERNE AYANT UNE ACTIVITE DE CANCEROLOGIE

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Résistance acquise ou intrinsèque des cellules cancéreuses coliques aux dérivés du platine

Le cisplatine (cis-diaminedichloroplatinum (II), CDDP) est un des médicaments anticancéreux les plus actifs dans les cancers humains, notamment ceux d'origine ovarienne ou testiculaire ; par contre, son efficacité est faible sur les cancers colorectaux. Les mécanismes gouvernant la sensibilité ou la résistance des tumeurs aux dérivés du platine sont mal connus. Dans ce travail, nous décrivons l'obtention de clones résistants au cisplatine dans deux modèles de cellules cancéreuses coliques, PROb (cellules cancéreuses coliques de rat) et HT29 (cellules cancéreuses coliques humaines) et analysons les mécanismes potentiels de la résistance dans les variants obtenus (CP33 et HT29-CP200). Les résultats obtenus nous ont tout d'abord permis d'éliminer plusieurs mécanismes proposés dans la littérature : phénomènes de transport ; mécanismes de détoxication ; modification des protéines régulant l'apoptose ou des protéines de stress [...]DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Osmolarité urinaire et nephrotoxicité du cisplatine

DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF