P Dufour

CHRU de Strasbourg, Strasburg, Alsace, France

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Publications (168)334.78 Total impact

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    ABSTRACT: Identify prognostic factors for survival and patterns of treatment failure after definitive radiochemotherapy for esophageal cancer. Between 2003 and 2006, 143 patients with squamous cell carcinoma and adenocarcinoma of the esophagus were retrospectively reviewed. Median age was 65 years (42-81). Median radiation dose was 62.5 Gy (38-72) with 1.8-2 Gy fraction. Median follow-up was 20.8 months (2.8-92.4). Three and 5-year local recurrence-free survival rates were 58.3% and 50.9%. In univariate analysis, traversable esophageal stricture was a prognostic factor. Three, 5-year locoregional recurrence-free survival rates were 42.4% and 34.9%. In multivariate analysis, traversable esophageal stricture and stage < IIB were independent prognostic factors. Three and 5-year disease-free survival rates were 30.5% and 25.9%. In multivariate analysis, Nutritional Risk Index (NRI) ≥ 97.5 and performance status (PS) = 0 were independent prognostic factors. Median, 3, and 5-year overall survival rates were 22.1 months, 34.4%, and 19.8%. In multivariate analysis, independent prognostic factors were NRI ≥ 97.5 and PS = 0. Median survival times for the NRI classes (no denutrition, moderate and severe denutrition) were 29.5, 19.7, and 12 months (P = 0.0004), respectively. A major impact of baseline NRI was found in terms of survival; it should be included in future prospective trials.
    Diseases of the Esophagus 10/2012; · 1.64 Impact Factor
  • Jean-Emmanuel Kurtz, Patrick Dufour
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    ABSTRACT: Despite its decreasing incidence in western countries, the care of gastric cancer remains a concern, as many patients are diagnosed with advanced disease. Whereas localized gastric cancer has benefited from advances in surgical management and perioperative chemotherapy, patients with unresectable or metastatic disease have a poor prognosis. However, advances in chemotherapy have still arisen, with the onset of more convenient and active schedules of treatment, but no significant breakthrough has been achieved in terms of survival. Recent trials in advanced gastric cancer have been focusing on targeted therapies. This article aims to focus on the current state of the art in terms of chemotherapy for advanced gastric cancer, as well as to describe and explain the rationale and hopes for newer therapies that are currently under investigation.
    Future Oncology 12/2011; 7(12):1441-50. · 3.20 Impact Factor
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    ABSTRACT: Although advanced prostate cancer patients respond very well to front-line androgen deprivation, failure to hormonal therapy most often occurs after a median time of 18-24 months. The care of castration-resistant prostate cancer (CRPC) has significantly evolved over the past decade, with the onset of first-line therapy with docetaxel. Although numerous therapy schedules have been investigated alongside docetaxel, in either first-line or salvage therapy, results were dismal. However, CRPC chemotherapy is currently evolving, with, on the one hand, new agents targeting androgen metabolism and, on the other hand, significant progress in chemotherapy drugs, particularly for second-line therapy. The aim of the present review is to describe the current treatments for CRPC chemotherapy alongside their challengers that might shortly become new standards. In this article, we discuss the most recent data from clinical trials to provide the reader with a comprehensive, state-of-the-art overview of CRPC chemotherapy and hormonal therapy.
    Oncology 05/2011; 80(1-2):1-11. · 2.17 Impact Factor
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    ABSTRACT: To assess the capacity of heavy ions to induce apoptosis in lymphocytes, mice have been irradiated with accelerated carbon ions (95 MeV/nucleon) at doses ranging from 0.1 to 4 Gy. Their spleens were removed 24 h later and gently dissociated to prepare a single cell suspension. Mononuclear cells were then maintained in culture at 37°C, and the occurrence of apoptosis in these cells was analysed 24 h later. Lymphocytes were also irradiated in vitro, in the presence of Ac-DEVD-CHO, a potent caspase-3 and -7 inhibitor. Results from three experiments performed at the Grand Accelerateur National d'Ions Lourds (GANIL, Caen, France) are reported here. They indicate that carbon ions induce a marked, dose-dependent, reduction of the spleen weight and cellularity. However, in sharp contrast with spleen cells prepared from X-ray irradiated mice, only a slight increase of apoptosis is evidenced in cultured lymphocytes from mice irradiated with heavy ions. The significance of such results is discussed. So far, few data exist concerning the biological effects of heavy ions, in particular their capacity to induce apoptosis in lymphocytes; the present study provides useful clues for further investigations.Key words : lymphocytes, apoptosis, heavy ions, splenic model, caspases.
    Canadian Journal of Physiology and Pharmacology 02/2011; 79(2):109-113. · 1.56 Impact Factor
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    ABSTRACT: Retrospective study of patients treated for high-grade glioma, with or without biodegradable carmustine wafers and according to the Stupp protocol. Between May 2007 and June 2008, 65 patients underwent surgery for high-grade glioma, 28 had implantation of Gliadel and 37 patients did not. Patients received radiotherapy with concomitant temozolomide followed by 5 consecutive days of temozolomide every month for 6 months. Overall median follow-up was 17.1 months; the median relapse-free survival (RFS) was 14 months with a RFS of 54% at 12 months, and 38% at 24 months. For patient with and without Gliadel, median and 1-year RFS were 12.9 months and 52% vs. 14 months and 42%, respectively (p = 0.89). According to pathology, Gliadel did not influence RFS of patients with Grade III or glioblastoma. However, for all patients, in multivariate analysis, non-methylated methylguanine methyltransferase (MGMT) was the only unfavorable prognostic factor of RFS (p = 0.017; HR 2.8; CI [1.2-7]). Median overall survival (OS) was 20.8 months; the OS rate at 12 months was 78.5%, and at 24 months 35.4%. For patients treated with and without Gliadel, median and 1-year OS were 20.6 months and 78.6% vs. 20.8 months and 78.4%, respectively. According to pathology, Gliadel did not influence OS of patients with Grade III or glioblastoma. For all patients, in multivariate analysis, unfavorable prognosticators for OS were non-methylated MGMT (p = 0.001; HR: 6.5; CI [2-20]) and irradiation dose <60 Gy (p = 0.02; HR: 6.3; CI [2-20]). With carmustine wafers, before irradiation, median gross tumor volume plus edema was 84 mL (27-229), whereas it was 68 mL (10-362) without carmustine (p = nonsignificant). Four cases of Grade 3 thrombopenia occurred, all in the carmustine wafer group. In patients with high-grade gliomas, adding Gliadel before performing a Stupp protocol did not improve survival.
    International journal of radiation oncology, biology, physics 02/2011; 82(2):749-55. · 4.59 Impact Factor
  • Jean-Emmanuel Kurtz, Patrick Dufour
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    ABSTRACT: In developing new anticancer drugs, the identification of relevant targets is a key issue of growing importance. Ideally, an anticancer drug target should be specific to cancer cells, in order to both increase efficacy and decrease toxicity of the compound. Epithelial cell adhesion molecule (EpCAM) is a membrane protein with proto-oncogenic properties that is expressed in a number of endothelium-derived cancers and is a promising anticancer drug target. Adecatumumab is a monoclonal, fully human IgG1 antibody that targets EpCAM, development of which is at present reaching Phase III trials. From a review of literature, we here update the rationale for using EpCAM as an anticancer target for monoclonal antibodies, with a special focus on adecatumumab. The fully human nature of adecatumumab is also discussed to put the drug in perspective with other related anti-EpCAM monoclonal antibodies, such as edrecolomab and catumaxomab. Adecatumumab studies are recapitulated, in order to provide the reader with a comprehensive view of the development of this promising anticancer agent. Adecatumumab is a promising fully human monoclonal antibody targeting EpCAM which is expressed in almost all adenocarcinomas and its activity is not dependent of K-Ras status.
    Expert opinion on biological therapy 06/2010; 10(6):951-8. · 3.22 Impact Factor
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    ABSTRACT: La réévaluation de la réponse tumorale après traitement radio-chimiothérapie néo-adjuvante ou exclusive est une étape clé dans la stratégie thérapeutique des carcinomes épidermoïdes de l’œsophage. Nous avons étudié la valeur de ll. L’œsophagoscopie de réévaluation pré-opératoire systématique dans la détection d’une tumeur résiduelle après traitement par radio-chimiothérapie. Patients et Méthodes Étude rétrospective de 95 patients porteurs d’un carcinome épidermoïde de l’œsophage de stade I à III traités par radio-chimiothérapie puis réévaluation avec œsophagoscopie puis œsophagectomie pour carcinome épidermoïde de l’œsophage de stade I à III. Les données macroscopiques et des biopsies systématiques de l’œsophagoscopie étaient comparées au résultat anatomo pathologique de la pièce opératoire. Les tests de Fischer, Student logrank et le modèle de Cox étaient employés pour évaluer la concordance entre résultats endoscopiques et anatomo-pathologiques et réaliser des analyses uni et multi-variée. Résultats Les résultats de l’endoscopie étaient corrélés aux résultats anatomo-pathologiques (p < 0,001) avec une sensibilité de 71,2 %, une spécificité de 100 %, une VPP de 100 % et une VPN de 60,4 %. Il n’existait pas de facteur prédictif de la réponse endoscopique en analyse multi-variée. Conclusions Dans ce travail, l’œsophagoscopie compte tenu de sa faible sensibilité concernant la détection de la maladie résiduelle ne peut être proposée pour identifier efficacement les patients ayant entièrement une réponse histologique complèterépondu à la radio-chimiothérapie.
    Ultrasound in Medicine and Biology - ULTRASOUND MED BIOL. 01/2010; 147(4):21-22.
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    ABSTRACT: Geriatric oncology is increasingly developing in Western countries as it is established that cancer peaks after 60 years of age, and the populations are inexorably aging. Aging is associated with a decrease in the use of chemotherapy, and some patients are therefore exposed to undertreatment. Comprehensive geriatric assessment is a composite of several scores that target the multidimensional aspects of the old person. With the use of comprehensive geriatric assessment, geriatricians and oncologists can tailor treatment to their patients. In this review, we briefly describe the characteristics of elderly cancer patients, and identify the pitfalls of anticancer treatment in elderly patients. In light of our expertise, we describe the benefits that can be awaited from joint efforts from geriatricians and oncologists and suggest future directions to answer unmet needs.
    Oncology 08/2009; 77(3-4):147-56. · 2.17 Impact Factor
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    ABSTRACT: A number of studies have shown that elderly cancer patients were denied optimal anticancer treatment because of age. Colorectal cancer is among the most frequent cancers in Western countries, and adjuvant chemotherapy has proven efficacy and tolerance in this condition. This study was undertaken to explore the current approaches to adjuvant chemotherapy in elderly cancer patients in a single institution. We retrospectively analyzed all patients' files that were discussed in the gastro-intestinal tumor board of the Hôpitaux Universitaires de Strasbourg during 3 years (2004-2006). The recorded variables included sex, age, tumor stage, cancer location colon vs rectum, number of comorbidities, occurrence of an oncogeriatric assessment, type and tolerance of chemotherapy. We investigated the reason to not administer adjuvant therapy in patients whom should have received this treatment if guidelines had to be applied. A total of 193 consecutive patients' files were extracted from colorectal cancer patients that had been discussed in the gastro-intestinal tumor board. Among these, we isolated patients over 70 years old who were proposed with either adjuvant chemotherapy (group A, n=65) or follow up (group B, n=128). The median age in group A was 75.3 years old. Tumor board recommendations were in accordance with guidelines in 91% of cases. Chemotherapy was delivered in 44 pts (76%) and completed in 42 (95%). The median age in group B was 78.6 years old, and in this group tumor board proposal met the guidelines in 83% of cases. In the logistic regression model, disease stage was the major variable leading to adjuvant treatment recommendation, age and comorbidities being of lesser importance. In our series, elderly colorectal cancer patients are not undertreated. Efforts should be maintained to educate physicians with regard to feasibility of adjuvant chemotherapy in elderly patients.
    Critical reviews in oncology/hematology 07/2009; 74(3):211-7. · 5.27 Impact Factor
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    ABSTRACT: To describe the patterns of care of elderly cancer patients (ECPs) (>70 years old) and the factors affecting the referral by general practitioners (GPs) of patients to cancer specialists (SPs), in Alsace France. A postal mail questionnaire was sent to a total of 2818 physicians including primary care physicians and specialists. The factors possibly responsible for a poor referral rate of ECPs and the factors affecting treatment implementation by specialists were explored. We also searched for unmet needs such as the incorporation of geriatric assessment into routine practice and continuous medical education (CME) programs. A total of 1217 questionnaires were returned (46.9%) from 1053 GPs and 214 SPs. Patients' age did not negatively impact referral to SPs as opposed to patients' performance status, wishes, and co-morbidities. Conversely, a significant decrease in patients' file presentation by SPs to tumor boards was observed for patients over 80 years old. Neither reimbursement nor SPs' waiting lists were an issue. The need for CME programs in geriatric oncology was emphasized by both GPs and SPs. Age was not the governing variable that impacted patient referral. The need for CME in geriatrics was highlighted for both GPs and SPs.
    Critical reviews in oncology/hematology 04/2009; 75(1):47-57. · 5.27 Impact Factor
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    ABSTRACT: Modern protocols of concomitant chemo/radiotherapy provide a very effective strategy to treat certain types of tumors. High-linear energy transfer (LET) radiations, on the other hand, have an increased efficacy against cancer with low radiosensibility and critical localization. We previously reported that oxaliplatin, a third generation platinum drug, was able to reinforce the cytotoxicity of an irradiation by fast neutrons towards human glioblastoma U-87 cells in culture. We show here that such a combination has the capacity to enhance the number of double strand breaks in DNA and to induce autophagy in these cells. Xenografts experiments were further performed in nude mice subcutaneously transplanted with U-87 cells. When injected shortly before a single irradiation by fast neutrons, oxaliplatin causes a marked reduction of tumor growth compared with the irradiation alone. Overall, our data indicate the unique cytotoxic mechanism of a combined high-LET irradiation and oxaliplatin treatment modality and suggest its potential application in anticancer therapy.
    Cancer Letters 07/2008; 264(1):63-70. · 5.02 Impact Factor
  • Journal de Chirurgie 05/2008; 145(3):289. · 0.50 Impact Factor
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    ABSTRACT: To investigate whether sinusoidal injury (SI) was associated with a worse outcome after hepatectomy in patients with colorectal liver metastases (CRLM). Correlation between SI and oxaliplatin-based chemotherapy (OBC) was recently shown in patients with CRLM. However, it has yet to be fully clarified whether SI affects liver functional reserve and outcome after hepatectomy. Between 2003 and 2005, 90 patients with CRLM who underwent an elective hepatectomy after preoperative chemotherapies were included. Diagnosis of SI was established pathologically in the nontumoral liver parenchyma of the resected specimens, and perioperative data were assessed in these patients. OBC was significantly associated with a higher incidence of SI. Preoperative indocyanine green retention rate at 15 minutes (ICG-R15) and postoperative value of total-bilirubin were significantly higher, and hospital stay was significantly longer in patients presenting with SI. Multivariate analysis showed that female gender, administration of 6 cycles or more of OBC, abnormal value of preoperative aspartate aminotransferase >36 IU/L, or abnormal value of preoperative ICG-R15 (>10%) were preoperative factors significantly associated with SI. Among patients undergoing a major hepatectomy, SI was significantly associated with higher morbidity and longer hospital stay. The present study suggests that SI resulted in a poorer liver functional reserve and in a higher complication rate after major hepatectomy. Therefore, female patients who received 6 cycles or more of OBC, or presenting with abnormal preoperative aspartate aminotransferase and ICG-R15 values should be carefully selected before deciding to undertake a major hepatectomy.
    Annals of Surgery 02/2008; 247(1):118-24. · 6.33 Impact Factor
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    ABSTRACT: To evaluate the outcome of patients treated for soft tissue sarcoma using three different post-operative radiotherapy schedules. Between 1990 and 2003, 89 patients (median age 50.8 years) presenting with soft tissue sarcoma (located to the limbs for 66 of them) underwent post-conservative-surgery radiotherapy. Pathology was liposarcoma in 35 cases and 54 others tumors. Tumors grades (FNCLCC classification) were 1, 2, 3 or unknown in 29, 32, 19 and 9 cases, respectively. Surgery was considered as complete in 68 patients. Irradiation was normofractionated (NF) in 62 cases, hyperfractionated (BF) in 19 cases and hypofractionated (HF) in 8 cases. For all the patients, median delivered dose was 61 Gy [34-76 Gy]. Median follow-up of alive patients was 73,8 months [3-184]. Five-year local control (LC) and overall survival (OS) rates were 85.5 and 71.2% respectively. According to multifactorial analysis, favourable prognostic factors were for local control, complete surgery (P=0.0075) and for overall survival, complete surgery (P=0.0267), grade 1 tumor (P=0.012) and absence of distant recurrence (P=0.0488). There was no statistical evidence of difference for the five-year LC and OS rates between the patients who received NF, BF or HF. There were few complications and there were comparable in the three groups. This retrospective serie showed similar results for all the schedules. There is no evidence to recommend bifractionation. Hypofractionation should be used only in selected patients with poor performans status.
    Cancer/Radiothérapie 01/2008; 11(8):443-51. · 1.48 Impact Factor
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    ABSTRACT: The effect of combining RDC-11 (a new ruthenium organometallic complex) and fast neutrons (high-LET radiations) has been evaluated in RDM4 and U-87 tumor cell lines. After co-treatment, a substantial reduction of cell growth was recorded, which appears not to be correlated with the induction of apoptosis.
    Letters in Drug Design &amp Discovery 12/2007; 5(1):1-6. · 0.85 Impact Factor
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    ABSTRACT: The combination of high-linear energy transfer (LET) radiation with chemotherapeutic agents may offer new perspectives in cancer treatment. We therefore assessed the consequences of a treatment in which U-87 human glioblastoma cells were irradiated with p(65)+Be neutrons in the presence of oxaliplatin, a third generation platinum anticancer drug having higher apoptosis-inducing activity than cisplatin. Cell survival, apoptosis, cell cycle progression as well as p21 and p53 protein expressions were analyzed. Results show that an enhanced cytotoxic effect was obtained when the two treatments were combined and that, unlike what we previously observed with cisplatin, this was not due to a reinforcement of apoptosis. Altogether, our results also indicate the potential of oxaliplatin for use in association with high-LET radiation against tumors refractory to conventional photon radiotherapy.
    Cancer Letters 09/2007; 254(1):54-62. · 5.02 Impact Factor
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    ABSTRACT: To compare the cost consequences of oral capecitabine and two different intravenous regimens of 5-fluorouracil/folinic acid (de Gramont and Mayo Clinic regimens) as adjuvant therapy in stage III colon cancer in France. Clinical efficacy and safety data were taken from published clinical trials. Medical resource use was estimated from published data and expert opinion. Direct costs (drug acquisition, inpatient and home drug administration, laboratory tests, transportation, and management of adverse events) were considered over a time horizon of 46 months (3.8 years). The perspective taken was that of the French Sickness Funds. In patients treated with capecitabine, relapse-free survival was 1.3 months longer than with the Mayo Clinic regimen, which has been shown to be as effective as the de Gramont regimen. In the base case analysis, capecitabine was less costly (3,654 EUR/patient) than the Mayo Clinic (10,481 EUR/ patient) and de Gramont (7,204 EUR/patient) regimens. In the sensitivity analysis, capecitabine remained dominant except when the intravenous regimens were assumed to be administered at home in all patients. In France, capecitabine is more effective and less costly than both the Mayo Clinic and de Gramont regimens as adjuvant therapy for colon cancer.
    Oncology 02/2007; 72(3-4):248-54. · 2.17 Impact Factor
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    ABSTRACT: To evaluate the efficacy and toxicity of pegylated liposomal doxorubicin (PLD; Caelyx)-cyclophosphamide combination in older metastatic breast cancer patients. A multicenter phase II trial was conducted. Inclusion criteria were age 65-75 years, ECOG 0-1 and left ventricular ejection fraction > or =50%. First-line chemotherapy was given to metastatic breast cancer patients resistant to hormonal therapy. The treatment schedule was PLD 40 mg/m(2) and cyclophosphamide 500 mg/m(2) on day 1 every 4 weeks. Efficacy was the primary endpoint, while response duration and tolerance were the secondary endpoints. Thirty-five patients (median age 71.3 years) were enrolled. No treatment-related death, no congestive heart failure or decrease in left ventricular ejection fraction and no febrile neutropenia were reported. Toxicity: grade 3 dyspnea was found in 1 patient, neutropenia in 11 patients (7 grade 3, 4 grade 4), grade 3 mucositis in 4 patients, grade 3 hand-foot syndrome in 1 patient and a generalized rash in 1 patient. An objective response (complete and partial response) was achieved in 10 (28.6%) patients and disease control in 24 (69%) with a progression-free survival of 8.8 months and a median overall survival of 20.3 months. The PLD-cyclophosphamide combination is moderately active and safe in elderly metastatic breast cancer patients, but cannot be recommended routinely due to myelotoxicity and mucositis hazards.
    Oncology 01/2007; 73(3-4):210-4. · 2.17 Impact Factor
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    ABSTRACT: PurposeTo evaluate the outcome of patients treated for soft tissue sarcoma using three different post-operative radiotherapy schedules.
    Cancer Radiotherapie - CANCER RADIOTHER. 01/2007; 11(8):443-451.
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    ABSTRACT: High linear energy transfer (LET) radiation have the ability to kill cancer cells resistant to conventional radiotherapy. On the other hand, protocols combining radiotherapy and chemotherapy are effective in eradicating certain inoperable cancers. In this study, we investigated the cytotoxicity of a co-treatment with fast neutrons and cisplatin in a human glioblastoma cell line, U-87. Cells cultured in vitro were irradiated with p(65)+Be neutrons in the presence of cisplatin. Cell survival and the induction of apoptosis and premature senescence were assessed at different time intervals thereafter, using a variety of methods. A marked reinforcement of the cytotoxicity was obtained when irradiation and cisplatin were associated. This reflected both an amplification of the apoptotic process and the induction of premature cell senescence. The efficiency of a combination between fast neutrons and cisplatin in inducing cell death in U-87 is more than additive. The present data concur with those we previously reported in a mouse lymphoma and suggest the potential utility of platinum compounds as adjuncts to future cancer therapy protocols using high-LET radiation.
    Life Sciences 08/2006; 79(6):513-8. · 2.56 Impact Factor

Publication Stats

1k Citations
334.78 Total Impact Points


  • 2000–2011
    • CHRU de Strasbourg
      Strasburg, Alsace, France
  • 1997–2009
    • Centre Paul Strauss
      Strasburg, Alsace, France
    • Institut Universitaire de France
      Lutetia Parisorum, Île-de-France, France
  • 2001–2008
    • Institut de Recherche contre les Cancers de l'Appareil Digestif
      Strasburg, Alsace, France
  • 1989–2001
    • University of Strasbourg
      • Faculty of Medicine
      Strasburg, Alsace, France