Montpellier, France
Montpellier, France

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Colombo P.E.,The Surgical Center | Patani N.,Specialty Registrar in General Surgery | Bibeau F.,Val dAurelle Anticancer Center | Assenat E.,Val dAurelle Anticancer Center | And 3 more authors.
Surgical Oncology | Year: 2011

Lymph node status at the time of diagnosis remains one of the principal indicators of prognosis in patients with rectal cancer. Involvement of loco-regional lymph nodes is relevant to surgical and clinical oncologists and continues to impact significantly upon local and systemic management strategies, in both neo-adjuvant and adjuvant settings. In this review, the clinical impact of lymph node status in the surgical management of rectal cancer is considered, with particular reference to the significance of lymphadenectomy and the potential implications for rectal tumours amenable to trans-anal excision. Current standards of care are reviewed and the extent to which the determination of lymph node status influences oncological decisions regarding neo-adjuvant and adjuvant therapies are discussed with areas of controversy highlighted. © 2011 Elsevier Ltd. All rights reserved.


Svobaite R.,Montpellier University | Svobaite R.,Kaunas University of Medicine | Svobaite R.,Val dAurelle Anticancer Center | Solassol I.,Val dAurelle Anticancer Center | And 6 more authors.
Journal of Liquid Chromatography and Related Technologies | Year: 2010

The objective of the present study was to develop a selective and sensitive liquid chromatography-mass spectrometry (LC-MS) method for the simultaneous quantitation of capecitabine, 5′-deoxy-5-fluorocytidine (5′-DFCR), 5′-deoxy-5-fluorouridine (5′-DFUR), 5-fluorouracil (5-FU), and 5-fluorodihydrouracil (5-FUH2) in human plasma. Chromatography was performed on an Atlantis dC18 column with a mobile phase consisting of 1% formic acid in acetonitrile and 1% formic acid in water gradient elution. 5-fluorocytosine (5-FC) was used as internal standard. LC-MS data were acquired in SIM mode at m/z 130 for 5-FC, m/z 131 for 5-FU, m/z 133 for 5-FUH2, m/z 246 for 5′-DFCR, m/z 247 for 5′-DFUR, and m/z 360 for capecitabine. The drug/internal standard peak area ratios were linked via quadratic relationships to concentrations (100-10000g/L for 5-FU; 50-10000g/L for 5-FUH2; and 25-10000g/L for 5′-DFCR, 5′-DFUR, and capecitabine). The analysis of blank matrices from different donors showed the absence of interfering endogenous components at the retention times of the analytes. No evidence of matrix effect was observed. The method was precise (precision, 0.2-8.3%) and accurate (recovery, 99-104%). Mean extraction efficiencies 89% for each analyte were obtained. The lower limits of quantitation were 25g/L for capecitabine, 5′-DFCR, and 5′-DFUR; 50g/L for 5-FUH2; and 100g/L for 5-FU. This method was successfully used to investigate plasma concentrations of capecitabine and its metabolites in a pharmacokinetic study carried out in patients with metastatic solid tumors receiving oral administration of capecitabine (1600 to 3420mg according to the patient) twice a day. Copyright © Taylor & Francis Group, LLC.


Kurtz J.-E.,Hautepierre Hospital | Freyer G.,Lyon Sud Hospital | Joly F.,Francois Baclesse Anticancer Center | Gladieff L.,Institute Claudius Regaud | And 7 more authors.
Anticancer Research | Year: 2012

Aim: Combined cisplatin-topotecan therapy is standard care for advanced cervical cancer, however it is associated with haematotoxicity and nephrotoxicity. This trial was designed to assess the combination of carboplatin which is less nephrotoxic, and oral topotecan. Patients and Methods: Patients with advanced/recurrent squamous cervical cancer received carboplatin (AUC5) on day 1, with escalating oral topotecan (3.0 mg/m 2 starting dose) on days 1, 8 and 15, every 4 weeks. Endpoints were the maximal tolerated dose for the phase I part and safety profiles and response rates for the phase II part of the study. Results: Two dose levels were evaluated. A total of 18 patients (6 phase I, 12 phase II) were treated. The maximal tolerated dose was 3.0 mg/m 2 topotecan with carboplatin AUC5. Phase II accrual was interrupted following unacceptable toxicity, with 10 therapy-related related serious events in 9 out of 12 patients: grade 3-4 pancytopenia (7), febrile neutropenia (1), grade 3 haemorrhage (1) and grade 3 vomiting (1). Conclusion: Weekly oral topotecan combined with carboplatin is associated with unmanageable toxicity and is not recommended. Future studies are warranted to better understand the toxicity of such a combination and explore alternative combinations for advanced cervical cancer.


Colombo P.-E.,The Surgical Center | Colombo P.-E.,Max Mousseron Institute of Biomolecules | Boustta M.,Max Mousseron Institute of Biomolecules | Poujol S.,Val dAurelle Anticancer Center | And 8 more authors.
Gynecologic Oncology | Year: 2011

Objective: Peritoneal spread is an adverse outcome in ovarian cancer. Despite clinical efficiency, intraperitoneal (i.p.) chemotherapy after cytoreductive surgery is associated with high systemic and local toxicity. Two polymer-drug delivery systems (P-HYD1-DOX and P-HYD2-DOX) were developed for i.p. administration by conjugating doxorubicin (DOX) to a poly(l-Lysine citramide) polymer carrier with a hydrazone-based degradable spacer. The aim of this study was to assess the antitumoral efficacy of these two conjugates in a xenograft model of human ovarian carcinomatosis. Methods: Peritoneal carcinomatosis was generated in athymic mice by i.p. injection of SKOV3-Luc cells. Free DOX, P-HYD1-DOX and P-HYD2-DOX solutions were administered i.p. at the same dose of 10 mg/kg (DOX eq.). For each treatment, tumor load and therapeutic efficacy were compared to untreated mice and assessed by bioluminescence imaging and survival rates. Toxicity profiles in each group and biodistribution of P-HYD2-DOX after i.p. administration were also determined. Results: P-HYD-1-DOX and P-HYD-2-DOX demonstrated significant antitumoral efficacy against peritoneal carcinomatosis. Compared to untreated group, P-HYD1-DOX improved median survival times from 58 to 105 days. For P-HYD2-DOX, median survival was not reached after a follow-up of 120 days. Bioluminescence showed high efficacy of P-HYD-2-DOX compared to free DOX but the difference was not significant. Biodistribution study confirmed that free and active DOX were successively released from P-HYD2-DOX in vivo. P-HYD-DOX conjugates were well tolerated by mice after i.p. injection. Conclusion: P-HYD-DOX conjugates demonstrated significant activity against peritoneal carcinomatosis in a xenograft model of ovarian carcinomatosis and their ability to release active DOX in i.p. deposits and tumor. These features are of clinical interest for i.p. administration in the treatment of ovarian peritoneal carcinomatosis after cytoreductive surgery. © 2011 Elsevier Inc.

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