Publications by authors named "Isabelle Trouilloud"

20 Publications

  • Page 1 of 1

Local treatment of pancreatic cancer metastases: A multicenter French study of the AGEO group.

Clin Res Hepatol Gastroenterol 2021 Mar 1;45(6):101607. Epub 2021 Mar 1.

Department of Oncology, Institute Mutualiste Montsouris, 42 Boulevard Jourdan, 75014 Paris, France.

Objective: This study reports the efficacy and safety of local treatment of metastases of pancreatic ductal adenocarcinoma (PDAC), with a curative intent.

Methods: We retrospectively included patients with histologically proven PDAC, who underwent a local treatment for metastases between January 1, 2000 and December 31, 2017, from 11 French hospitals. Complications of local treatment were reported. Univariate Cox models were performed to identify prognosis factors associated with overall survival (OS) and disease-free survival (DFS).

Results: We included 52 patients treated for 68 metastases; 33 (64%) of whom had metachronous metastases. Metastatic sites treated were: 39 (57%) hepatic, 18 (27%) pulmonary and 11 (16%) others. Metastases treatments were: 45 (66%) surgery, 9 (13%) radiofrequency and 14 (21%) other procedures. The rates of severe complications and mortality were respectively 10% and 4%. The median OS and DFS after local treatment were 36.5 months and 12.7 months, respectively. Prognosis factors associated with a shorter OS were: liver metastases when compared with lung metastases (HR 4.04; 95%CI: 1.18-13.81), N2 status of primary pancreatic tumor when compared to N0-N1 (HR 9.43; 95%CI: 2.44-36.36) and synchronous metastases when compared to metachronous metastases (HR 2.34; 95%CI: 1.05-5.23). N2 status of primary pancreatic tumor was associated with a shorter DFS when compared to N0-N1 (HR 2.82; 95%CI: 1.05-7.58).

Conclusion: In this series of highly selected patients, local treatment of metastases from PDAC is associated with prolonged survival. The rate of severe complications was low. Factors associated with shorter OS were liver metastases, N2 status and synchronous metastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2020.101607DOI Listing
March 2021

Prognostic value of the early change in neutrophil-to-lymphocyte ratio in metastatic pancreatic adenocarcinoma.

Clin Res Hepatol Gastroenterol 2020 Oct 11:101541. Epub 2020 Oct 11.

Sorbonne Université, 4 Place Jussieu, 75005, Paris, France; Department of Hepato-Gastroenterology, Hôpital Pitié-Salpêtrière, 47 Boulevard de l'Hôpital 75013, APHP, Paris, France. Electronic address:

In metastatic pancreatic adenocarcinoma, a high neutrophil-to-lymphocyte ratio (NLR) at diagnosis is a marker of poor prognosis. The prognostic role of baseline NLR and NLR change during first-line chemotherapy were determined. We conducted a retrospective study by using data from a single-center prospective cohort and a randomized open-label, multicenter, randomized trial. Two hundred and twelve patients were analyzed. Baseline NLR>5 was an independent marker of poor prognosis for overall survival (HR=2.01, 95% CI 1.33-3.05; P=0.001) and progression-free survival (PFS; HR=1.80, 95% CI 1.23-2.65; P=0.0026). According to NLR dynamics (n=172), patients with NLR≤5 on days 1 and 15 had a significantly better prognosis than those with NLR≤5 on day 1 and NLR>5 on day 15 (HR=2.23, 95% CI 1.18-4.21; P=0.013), NLR >5 on day 1 and NLR ≤5 on day 15 (HR=3.25, 95% CI 1.86-5.68; P<0.001), and NLR>5 on days 1 and 15 (HR=3.37, 95% CI 1.93-5.90; P<0.001). Over time, bad responders (PFS <6 months) had significantly higher mean NLR than good responders (PFS>6 months; group effect: P<0.0001). Seven out of eight patients with baseline NLR>5 had circulating tumor DNA. This study confirmed the independent prognostic value of baseline NLR >5 in metastatic pancreatic cancer. The change in NLR early during chemotherapy was also a prognostic indicator in patients with NLR ≤5.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2020.08.016DOI Listing
October 2020

Reasons for chemotherapy discontinuation and end-of-life in patients with gastrointestinal cancer: A multicenter prospective AGEO study.

Clin Res Hepatol Gastroenterol 2021 Jan 11;45(1):101431. Epub 2020 May 11.

Department of hepatogastroenterology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, 47-83, boulevard de l'Hôpital, 75013 Paris, France.

Background: Previous research on chemotherapy discontinuation has mainly focused on predictive factors and outcomes. Few data are available on the reasons for chemotherapy discontinuation. The main objective was to identify the reasons for chemotherapy discontinuation in patients with gastrointestinal cancer. The secondary objectives were to describe the announcement of chemotherapy discontinuation and the time between chemotherapy discontinuation and death.

Methods: This prospective multicenter French cohort included patients with advanced gastrointestinal cancer, for whom chemotherapy was discontinued between May 2016 and January 2018.

Results: One hundred and fourteen patients were analyzed. The first cause of chemotherapy discontinuation was the impairment of general condition (asthenia, cachexia). Complications such as sepsis, jaundice or occlusion, were the second most frequent cause. Progression was observed at chemotherapy discontinuation in two-thirds of cases. The announcement of the chemotherapy discontinuation was made formally in 74% of cases, with a follow-up by a palliative care team initiated in 50% of cases. Sixty-nine percent of the patients received chemotherapy during the last three months of life and 26% during the last month. The median time between chemotherapy discontinuation and death was 65 days (IQR: 36.5-109): 44% of patients died at the hospital, 39% in a palliative care unit and 16% at home.

Conclusion: Impairment of general condition was the major reason for chemotherapy discontinuation in patients with gastrointestinal cancers. Complications such as jaundice, sepsis or occlusion, were important reasons for discontinuation and could explain our shorter time between chemotherapy discontinuation and death, compared to other oncology sub-specialties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2020.03.029DOI Listing
January 2021

Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study).

Oncologist 2020 02 2;25(2):e266-e275. Epub 2019 Oct 2.

Department of Gastroenterology, Cochin Hospital, Paris, France.

Background: Patients with RAS wild-type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti-epidermal growth factor receptor (EGFR) combined with first-line, 5-fluorouracil-based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti-EGFR. Our objective was to compare both strategies in a routine practice setting.

Materials And Methods: This multicenter, retrospective, propensity score-weighted study included patients with a RAS WT nonresectable mCRC, treated between 2013 and 2016 by a 5-FU-based chemotherapy, with either delayed anti-EGFR or immediate anti-vascular endothelial growth factor (VEGF). Primary criterion was overall survival (OS). Secondary criteria were progression-free survival (PFS) and objective response rate (ORR).

Results: A total of 262 patients (129 in the anti-VEGF group and 133 in the anti-EGFR group) were included. Patients receiving an anti-VEGF were more often men (68% vs. 56%), with more metastatic sites (>2 sites: 15% vs. 9%). The median delay to obtain the RAS status was 19 days (interquartile range: 13-26). Median OS was not significantly different in the two groups (29 vs. 30.5 months, p = .299), even after weighting on the propensity score (hazard ratio [HR] = 0.86, 95% confidence interval [CI], 0.69-1.08, p = .2024). The delayed introduction of anti-EGFR was associated with better median PFS (13.8 vs. 11.0 months, p = .0244), even after weighting on the propensity score (HR = 0.74, 95% CI, 0.61-0.90, p = .0024). ORR was significantly higher in the anti-EGFR group (66.7% vs. 45.6%, p = .0007).

Conclusion: Delayed introduction of anti-EGFR had no deleterious effect on OS, PFS, and ORR, compared with doublet chemotherapy with anti-VEGF.

Implications For Practice: For RAS/RAF wild-type metastatic colorectal cancer, patients may receive 5-fluorouracil-based chemotherapy plus either bevacizumab or an anti-epidermal growth factor receptor (EGFR). In daily practice, the time to obtain the RAS status might be long enough to consider two options: to start the chemotherapy with bevacizumab, or to start without a targeted therapy and to add the anti-EGFR at reception of the RAS status. This study found no deleterious effect of the delayed introduction of an anti-EGFR on survival, compared with the introduction of an anti-vascular endothelial growth factor from cycle 1. It is possible to wait one or two cycles to introduce the anti-EGFR while waiting for RAS status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2019-0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011620PMC
February 2020

Three fluoropyrimidine-based regimens in routine clinical practice after nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer: An AGEO multicenter study.

Clin Res Hepatol Gastroenterol 2020 06 10;44(3):295-301. Epub 2019 Oct 10.

Department of Gastroenterology and Digestive Oncology, Georges-Pompidou European Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), Sorbonne Paris Cité Paris Descartes University, Paris, France.

Background: A combination of nab-paclitaxel plus gemcitabine (N+G) has recently become a standard first-line treatment in patients with metastatic pancreatic adenocarcinoma (MPA), but there are currently no published data concerning second-line treatment after N+G. The aim of this study was to evaluate the survival outcomes and tolerability of three usual fluoropyrimidine-based regimens FOLFOX, FOLFIRI and FOLFIRINOX after N+G failure in MPA patients.

Methods: Patients receiving N+G as first-line regimen were prospectively identified in 11 French centers between January 2014 and January 2017. After disease progression or unacceptable toxicity, patients eligible for second-line therapy were enrolled in the study. The primary endpoint was overall survival following the second-line regimen. Secondary endpoints were objective response, progression-free survival and safety.

Results: Out of 137 patients treated with N+G as first-line regimen, 61 (44.5%) received second-line chemotherapy, including FOLFOX (39.4%), FOLFIRI (34.4%) or FOLFIRINOX (26.2%). Baseline characteristics were not different between the 3 groups. In particular, median age was 71.7 years, sex ratio was 1/1, and performance status (PS) was 0 in 11.5% of case. Main grade 3 toxicities were neutropenia (4.9%) and nausea (3.3%), without major differences between the groups. No toxic death was observed. Median second-line progression-free survival (PFS) and overall survival (OS) were 2.95 (95% CI: 2.3-5.4) and 5.97 months (95% CI: 4.0-8.0), respectively, with no difference between the 3 groups. Median OS from the start of first-line chemotherapy was 12.7 months (10.4-15.1) and was significantly better in patients receiving FOLFIRI after N+G failure, 18.4 months (95% CI: 11.7-24.1, P<0.05), as compared with FOLFOX or FOLFIRINOX (10.4 and 12.3 months, respectively).

Conclusion: This study suggests that second-line fluoropyrimidine-based regimens after N+G failure are feasible, have a manageable toxicity profile in selected patients with MPA, and are associated with promising clinical outcomes, in particular when combined with irinotecan. Randomized phase 3 trials are needed to confirm this trend.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2019.08.009DOI Listing
June 2020

Folfirinox gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study.

Therap Adv Gastroenterol 2019 25;12:1756284819878660. Epub 2019 Sep 25.

Department of Gastroenterology and Gastro-intestinal Oncology, Hôpital Européen Georges-Pompidou, APHP, Paris Descartes University, Sorbonne Paris Cité, Paris, France.

Background: Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce.

Methods: Data from two independent cohorts enrolling patients treated with FFX ( = 107) or GN ( = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable.

Results: In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10-21) than in GN groups (9 months; 95% CI: 8-12) before ( = 0.008) and after ( = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months;  = 0.053). After matching ( = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67;  = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX-GN sequence) was higher (46.9%) than the reverse sequence (20.4%;  = 0.01), which suggests a higher feasibility for the FFX-GN sequence. Corresponding median OS were 19 months 9.5 months, respectively ( = 0.094).

Conclusion: This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1756284819878660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764033PMC
September 2019

Characteristic and outcomes of patients with pathologic complete response after preoperative treatment in borderline and locally advanced pancreatic adenocarcinoma: An AGEO multicentric retrospective cohort.

Clin Res Hepatol Gastroenterol 2019 11 24;43(6):663-668. Epub 2019 Apr 24.

Sorbonne Paris-Cité, Paris Descartes University, hepatogastroenterology and gastrointestinal oncology department, hôpital Européen Georges-Pompidou, 75015 Paris, France. Electronic address:

Introduction: Following publication of improved patients' outcome using first line FOLFIRINOX for metastatic pancreatic adenocarcinoma, many physicians now prescribe it as neo-adjuvant or induction treatment for borderline and locally advanced pancreatic cancer. A pathologic complete response, rarely seen with previous preoperative regimens, is sometimes observed in these patients. The aim of this study was to assess long-term outcomes of patients presenting pathologic complete response after preoperative FOLFIRINOX usually followed by chemo-radiation therapy for non-metastatic pancreatic adenocarcinoma.

Material And Methods: We retrospectively identified all resected patients with pancreatic cancer presenting pathologic complete response after FOLFIRINOX in 9 French centers from the AGEO group between November 2010 and May 2017.

Results: 29 patients were enrolled, 14 had borderline, 14 locally advanced and 1 oligo-metastatic pancreatic cancer. M/F ratio was 1.2 and the mean age was 57 years. All patients were treated with FOLFIRINOX (n = 29), de-escalated to gemcitabine (n = 1) and FOLFIRI (n = 2), and 24 (83 %) received radiation therapy after chemotherapy. Objective response rate to preoperative chemotherapy was 66% (RECIST V1.1). Only 8 patients received postoperative chemotherapy. After a median follow-up of 34 months from surgery, the median overall survival was not reached and the median disease free survival was 48 months. The 1-year and 2-year survival rates were 100% for OS and 96% and 72 % for DFS from surgery, 8 of the 9 observed recurrences were distant metastases.

Conclusions: The promising 1 and 2-year overall survival and disease free survival rates suggest that pathologic complete response is a major prognostic factor in resected pancreatic cancer following preoperative chemo-radiotherapy. A longer follow-up and prospective series are now necessary to confirm these encouraging results and to potentially validate pathologic complete response as a relevant surrogate marker of preoperative treatment efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2019.03.007DOI Listing
November 2019

Immunotherapy and metastatic colorectal cancers with microsatellite instability or mismatch repair deficiency.

Bull Cancer 2019 Feb 14;106(2):137-142. Epub 2018 Oct 14.

AP-HP, Sorbonne université, hôpital Saint-Antoine, department of medical oncology, 75012 Paris, France.

Microsatellite instability (MSI) is a molecular indicator of defective DNA mismatch repair (dMMR) and is observed in approximately 5% of metastatic colorectal cancers (mCRC). MSI is a major predictive biomarker for the efficacy of immune checkpoint inhibitors (ICKi) amongst mCRC patients. After summarizing the literature about the efficacy of conventional cytotoxic regimens, we will highlight studies that have demonstrated the clinical activity of ICKi for patients with chemoresistant MSI/dMMR mCRC. Then we will focus on ongoing clinical trials and emerging challenges for the treatment of patients with MSI/dMMR mCRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bulcan.2018.09.004DOI Listing
February 2019

Immunotherapy and patients treated for cancer with microsatellite instability.

Bull Cancer 2017 Jan 13;104(1):42-51. Epub 2016 Dec 13.

Department of Medical Oncology, Hôpital Saint-Antoine, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, France. Electronic address:

Microsatellite instability (MSI) is a tumor phenotype linked to somatic or germline (Lynch syndrome) inactivating alterations of DNA mismatch repair genes. A broad spectrum of neoplasms exhibits MSI phenotype, mainly colorectal cancer, endometrial cancer, and gastric cancer. MSI tumors are characterized by dense immune infiltration and high load of tumor neo-antigens. Growing evidence is accumulating on the efficacy of immune checkpoint inhibition for patients treated for MSI solid tumors. We present a comprehensive overview of MSI phenotype, its biological landscape and current diagnostic methods. Then we focus on MSI as a predictive biomarker of response to immune checkpoint inhibition in the context of colorectal cancer and non-colorectal tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bulcan.2016.11.006DOI Listing
January 2017

[New molecular classification of colorectal cancer, pancreatic cancer and stomach cancer: Towards "à la carte" treatment?].

Bull Cancer 2016 Jul-Aug;103(7-8):643-50. Epub 2016 Jun 23.

Hôpital Saint-Antoine, service d'oncologie médicale, Paris, France; Université Pierre-et-Marie-Curie (UPMC), 75013 Paris, France. Electronic address:

This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion). In gastric adenocarcinoma, 4 groups were established: subtype "EBV" (9%, high frequency of PIK3CA mutations, hypermetylation and amplification of JAK2, PD-L1 and PD-L2), subtype "MSI" (22%, high rate of mutation), subtype "genomically stable tumor" (20%, diffuse histology type and mutations of RAS and genes encoding integrins and adhesion proteins including CDH1) and subtype "tumors with chromosomal instability" (50%, intestinal type, aneuploidy and receptor tyrosine kinase amplification). In pancreatic adenocarcinomas, a classification in four sub-groups has been proposed, stable subtype (20%, aneuploidy), locally rearranged subtype (30%, focal event on one or two chromosoms), scattered subtype (36%,<200 structural variation events), and unstable subtype (14%,>200 structural variation events, defects in DNA maintenance). Although currently away from the care of patients, these classifications open the way to "à la carte" treatment depending on molecular biology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bulcan.2016.05.007DOI Listing
January 2017

Efficacy of Adjuvant Chemotherapy in Colon Cancer With Microsatellite Instability: A Large Multicenter AGEO Study.

J Natl Cancer Inst 2016 Jul 1;108(7). Epub 2016 Feb 1.

Affiliations of authors: Department of Gastroenterology (DT, GS, CS), Department of Medical Oncology (AF), and Department of Molecular Oncology (LKT), Poitiers University Hospital , Poitiers , France ; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC) - EA 4331, Poitiers University , Poitiers (DT, CS); Methodology and Quality of Life in Oncology Unit, Besançon University Hospital , Besançon , France (GM); Department of Gastroenterology, Ambroise Paré Hospital , Boulogne-Billancourt , France (IT); Department of Gastroenterology (TL) and Department of Biochemistry (JCP), Tours University Hospital , Tours , France , UMR GICC CNRS 7292, Tours François Rabelais University, Tours (TL); Paris Descartes University, Cochin Hospital , Paris , France (RC); Department of Gastroenterology (TA) and Department of Medical Oncology (CDG), Avicenne Hospital , Bobigny , France ; Department of Gastroenterology, Bordeaux Nord Aquitaine Clinic , Bordeaux , France (CL); Department of Gastroenterology, Jean Mermoz Lyon Hospital , Lyon , France (PA); Department of Gastroenterology, Nantes University Hospital , Nantes , France (EC, TMB); Department of Gastroenterology, Rouen University Hospital , Rouen , France (DS, PM); Department of Medical Oncology, Saint-Antoine Hospital , Paris , France (TB); Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, APHP , Paris , France (JT, AZ); Paris Descartes University, Sorbonne Paris Cité , Paris , France (RC, JT, AZ).

Background: Deficient mismatch repair (dMMR) colon cancer (CC) is reportedly resistant to 5-fluorouracil (5FU) adjuvant chemotherapy while preliminary data suggest chemosensitivity to oxaliplatin. We assessed the efficacy of fluoropyrimidine with and without oxaliplatin in a large cohort of dMMR CC patients.

Methods: This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for stage II or III dMMR CC between 2000 and 2011. Prognostic factors were analyzed using Cox models, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided.

Results: A total of 433 dMMR CC patients were included (56.8% stage II, 43.2% stage III). Mean follow-up was 47.0 months. The patients received surgery alone (n = 263) or surgery plus adjuvant chemotherapy consisting of fluoropyrimidine with (n = 119) or without (n = 51) oxaliplatin. Adjuvant chemotherapy was administered to 16.7% of stage II and 69.0% of stage III CC patients. As compared with surgery alone, adjuvant oxaliplatin-based chemotherapy improved disease-free survival (DFS) in multivariable analysis (HR = 0.35, 95% CI = 0.19 to 0.65, P < .001), contrary to adjuvant fluoropyrimidine alone (HR = 0.73, 95% CI = 0.36 to 1.49, P = .38). In the subgroup analysis, the DFS benefit of oxaliplatin-based chemotherapy was statistically significant in multivariable analysis only in stage III (HR = 0.41, 95% CI = 0.19 to 0.87, P = .02).

Conclusion: This study supports the use of adjuvant chemotherapy with fluoropyrimidine plus oxaliplatin in stage III dMMR CC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djv438DOI Listing
July 2016

Pathologic Major Response After FOLFIRINOX is Prognostic for Patients Secondary Resected for Borderline or Locally Advanced Pancreatic Adenocarcinoma: An AGEO-FRENCH, Prospective, Multicentric Cohort.

Ann Surg Oncol 2015 Dec 14;22 Suppl 3:S1196-205. Epub 2015 Aug 14.

Gastroenterology and Digestive Oncology Department, Pitié-Salpêtrière Hospital, Sorbonne University, UPMC University, Paris, France.

Purpose: In view of increased response rates and survivals in patients with metastatic pancreatic adenocarcinoma (PAC) with FOLFIRINOX, many centers proposed this regimen as induction chemotherapy for borderline (BR) or locally advanced (LA) PAC. The aim of this study was to assess surgical and oncological outcomes of patients who underwent resection after induction FOLFIRINOX therapy.

Methods: We prospectively identified surgical consecutive BR or LA PAC patients after induction FOLFIRINOX in 20 observational French centers between November 2010 and December 2013. Two independent experts retrospectively evaluated initial CT scan for central review.

Results: Eighty patients were included, 47 had BR and 33 had LA PAC. Median number of FOLFIRINOX cycles was 6 (range 1-30) and 65 % of patients received chemoradiation. The 30-day-mortality, major complications, and symptomatic pancreatic fistula rates were 2.5, 22.5, and 4 %, respectively. R0 resection was achieved in 84 %. After a median follow-up of 38.2 months since diagnosis, disease-free survival (DFS) was 17.16 months. The overall survival rates at 12 and 24 months were 92 and 81 %, respectively. A 26 % (n = 21) pathologic major response (pMR) rate was reached. In univariate and multivariate analysis, pMR was a prognostic factor for DFS (hazard ratio 0.33; P = 0.01 and hazard ratio 0.38; P = 0.035).

Conclusions: Resection after induction FOLFIRINOX is safe and associated with similar or better outcomes as upfront surgery in patients with PAC. A pMR was observed in 26 % of cases and was prognostic of DFS. This therapeutic design should be investigated in prospective studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-015-4783-xDOI Listing
December 2015

Second-line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine-platinum combination: A large multicenter study by the Association des Gastro-Entérologues Oncologues.

Cancer 2015 Sep 5;121(18):3290-7. Epub 2015 Jun 5.

Department of Medical Oncology, René Huguenin Hospital, Curie Institute, Saint-Cloud, France.

Background: Few data are available on second-line chemotherapy (CT2) for advanced biliary tract cancer (ABTC). The aim of this multicenter study was to describe the CT2 regimens used, the response rates, and the outcomes of patients treated with various CT2 regimens.

Methods: Patients who received CT2 for ABTC at 17 French institutions after the failure of the gemcitabine-platinum combination were retrospectively studied. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method. Cox models were used for multivariate analyses.

Results: Among 603 patients who received first-line chemotherapy (CT1) for ABTC, 196 received CT2: 5-fluorouracil (5-FU) and irinotecan (n = 64), 5-FU and oxaliplatin (n = 21), 5-FU and cisplatin (n = 38), 5-FU or capecitabine (n = 40), sunitinib (n = 10), or other various regimens (n = 23). Among the 186 assessable patients, there were 22 partial responses and 70 stabilizations. After a median follow-up of 26.4 months, the median PFS and OS were 3.2 and 6.7 months, respectively. There was no significant difference in PFS or OS between CT2 regimens. Fluoropyrimidine-based doublet chemotherapy was not superior to fluoropyrimidine alone in terms of OS and PFS. In a multivariate analysis, a performance status of 0 to 1, disease control with CT1, and a carbohydrate antigen 19-9 (CA 19-9) level ≤ 400 IU/mL were significantly associated with longer PFS and OS. Grade 3 to 4 toxicity occurred in 32% of the patients.

Conclusions: CT2 might provide disease control for selected patients with ABTC after the failure of gemcitabine-platinum, but the prognosis remains poor. No particular regimen seems superior to others, and this calls for new treatments. A good performance status, disease control with CT1, and a low level of CA 19-9 were associated with longer survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.29471DOI Listing
September 2015

Sequential FOLFIRI.3 + Gemcitabine Improves Health-Related Quality of Life Deterioration-Free Survival of Patients with Metastatic Pancreatic Adenocarcinoma: A Randomized Phase II Trial.

PLoS One 2015 26;10(5):e0125350. Epub 2015 May 26.

National Quality of Life in Oncology Platform, Besançon, France; Methodological and Quality of Life in Oncology Unit (EA 3181), University Hospital of Besançon, Besançon, France.

Background: A randomized multicenter phase II trial was conducted to assess the sequential treatment strategy using FOLFIRI.3 and gemcitabine alternately (Arm 2) compared to gemcitabine alone (Arm 1) in patients with metastatic non pre-treated pancreatic adenocarcinoma. The primary endpoint was the progression-free survival (PFS) rate at 6 months. It concludes that the sequential treatment strategy appears to be feasible and effective with a PFS rate of 43.5% in Arm 2 at 6 months (26.1% in Arm 1). This paper reports the results of the longitudinal analysis of the health-related quality of life (HRQoL) as a secondary endpoint of this study.

Methods: HRQoL was evaluated using the EORTC QLQ-C30 at baseline and every two months until the end of the study or death. HRQoL deterioration-free survival (QFS) was defined as the time from randomization to a first significant deterioration as compared to the baseline score with no further significant improvement, or death. A propensity score was estimated comparing characteristics of partial and complete responders. Analyses were repeated with inverse probability weighting method using the propensity score. Multivariate Cox regression analyses were performed to identify independent factors influencing QFS.

Results: 98 patients were included between 2007 and 2011. Adjusting on the propensity score, patients of Arm 2 presented a longer QFS of Global Health Status (Hazard Ratio: 0.52 [0.31-0.85]), emotional functioning (0.35 [0.21-0.59]) and pain (0.50 [0.31-0.81]) than those of Arm 1.

Conclusion: Patients of Arm 2 presented a better HRQoL with a longer QFS than those of Arm 1. Moreover, the propensity score method allows to take into account the missing data depending on patients' characteristics.

Trial Registration Information: Eudract N° 2006-005703-34. (Name of the Trial: FIRGEM).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0125350PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444351PMC
February 2016

Fixed-dose rate gemcitabine alone or alternating with FOLFIRI.3 (irinotecan, leucovorin and fluorouracil) in the first-line treatment of patients with metastatic pancreatic adenocarcinoma: an AGEO randomised phase II study (FIRGEM).

Eur J Cancer 2014 Dec 17;50(18):3116-24. Epub 2014 Oct 17.

Hôpital Européen Georges Pompidou, Université Paris Descartes, Paris, France. Electronic address:

Background: Fluorouracil and irinotecan-based, and gemcitabine-based regimens, are the standard of care in the first-line treatment of patients with metastatic pancreatic cancer. New approaches are needed to improve survival and quality of life. Whether a sequential approach alternating irinotecan, fluorouracil and gemcitabine may be effective and tolerable in patients with metastatic pancreatic cancer is unknown.

Methods: In this randomised, multicentre, open-label, phase 2 trial, patients with metastatic pancreatic adenocarcinoma, World Health Organisation (WHO) performance status 0-1, and bilirubin levels <1.5 upper limit of normal values (ULN) were randomised 1:1 to receive as first-line treatment either FOLFIRI.3 (irinotecan, leucovorin and fluorouracil) alternating with fixed-dose rate gemcitabine as 2-month periods (FIRGEM, arm A), or fixed-dose rate gemcitabine alone (arm B). Treatment was continued until disease progression or limiting toxicity. The primary end-point was the crude progression-free survival (PFS) rate at 6 months. The study is registered with EudraCT (N° 2006-005703-34).

Results: Between October 2007 and March 2011, 98 patients were enroled. The observed 6-month PFS rate was 43.5% (95% confidence interval (CI), [28.6-58.4%]) in arm A reaching the Fleming decision rules criteria to reject H0 and 26.1% (95% CI [12.9-39.3%]) in arm B. Objective response rates were 37% (23-51%) in arm A and 10% (1-19%) in arm B. Median PFS (5.0 versus 3.4 months, hazard ratio (HR)=0.59 [0.38-0.90]) and overall survival (11.0 versus 8.2 months, HR=0.71 [0.46-1.10]) were higher in arm A compared to arm B. The most frequent grade 3-4 toxicities were neutropenia (49%/24%; febrile neutropenia, 4%/0% in arms A/B), diarrhoea (arm A, 12% and arm B, 0%), and nausea/vomiting (8%/4%). No toxic deaths occurred.

Conclusion: The FIRGEM strategy appears to be effective and feasible in patients with metastatic pancreatic cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2014.09.015DOI Listing
December 2014

FOLFOX as second-line chemotherapy in patients with pretreated metastatic pancreatic cancer from the FIRGEM study.

BMC Cancer 2014 Jun 14;14:441. Epub 2014 Jun 14.

Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, AP-HP, 20 rue Leblanc, 75015 Paris, France.

Background: FOLFOX second-line treatment seems to be a validated option for patients with pancreatic cancer (PC) progressing after gemcitabine chemotherapy. However, other therapeutics strategy has developed in first-line therapy, as the FIRGEM phase II study that evaluated gemcitabine alone versus FOLFIRI.3 alternating with gemcitabine every two months. The present study assessed the efficacy and safety of FOLFOX after failure of the first-line therapy used in the FIRGEM study.

Methods: In this prospective observational cohort study, we analysed all consecutive patients who received second-line chemotherapy with FOLFOX among 98 patients with metastatic PC included in the FIRGEM study. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of second-line chemotherapy using the Kaplan-Meier method.

Results: Among 46 patients who received second-line chemotherapy, 27 patients (male, 55%; median age, 61 years; performance status (PS) 0-1, 44%) were treated with FOLFOX after progression to first-line gemcitabine alone (n = 20) or FOLFIRI.3 alternating with gemcitabine (n = 7). Grade 3 toxicity was observed in 33% of patients (no grade 4 toxicity). At the end of follow-up, all patients had progressed and 25 had died. No objective response was observed, and disease control rate was 36%. Median PFS and OS were 1.7 and 4.3 months, respectively. In multivariate analysis, PS was the only independent prognostic factor. For patients PS 0-1 versus 2-3, median PFS was 3.0 versus 1.2 months (log rank, p = 0.002), and median OS was 5.9 versus 2.6 months (log rank, p = 0.001).

Conclusions: This study suggests that FOLFOX second-line therapy offered interesting efficacy results with an acceptable toxicity profile in metastatic PC patients with a good PS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2407-14-441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075567PMC
June 2014

Chemosensitivity in ovarian metastases from gastric cancer: a case series.

Clin Res Hepatol Gastroenterol 2013 Jun 9;37(3):289-95. Epub 2012 Nov 9.

Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, University of Paris Descartes, 20, rue Leblanc, 75015 Paris, France.

The development of ovarian metastases from gastric cancer indicates a turning point of the disease progression and is usually associated with poor prognosis. Efficacy of modern chemotherapy protocols in ovarian metastases from gastric cancer is unknown. In this case series, we have evaluated the chemosensitivity of ovarian metastases from gastric cancer in eight consecutive patients treated in our institution between January 2000 and April 2012. Median age at gastric cancer diagnosis was 48.3 years and ovarian metastases were mainly metachronous (88%). Patients were treated with FOLFOX or FOLFIRI protocols in first-line and with EOX protocol in second-line chemotherapy. These protocols of chemotherapy used in first- and second-line treatment were able to control the disease in 33.3% for ovarian metastases compared to 66.7% for extraovarian metastases. Mean overall survival (OS) from ovarian metastases diagnosis was 14.2 months. The four patients treated by bilateral oophorectomy had a longer mean OS (16 months) than the four patients who did not experienced surgery (12.3 months). In conclusion, this case series suggests that ovarian metastases from gastric cancer are less sensitive than extraovarian metastases to modern protocol of chemotherapy. To confirm these observations, a large retrospective study is ongoing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2012.09.007DOI Listing
June 2013

Effectiveness of combined endoscopic ultrasound-guided fine-needle aspiration biopsy and stenting in patients with suspected pancreatic cancer.

Eur J Gastroenterol Hepatol 2012 Nov;24(11):1281-7

Department of aGastroenterology, Hopital Cochin, Paris, France.

Background: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) can be coupled with endoscopic retrograde cholangiopancreatography in the same setting when biliary and/or duodenal stenting are required.

Aims: Our aim was to examine the effectiveness of EUS-FNA combined with stenting during the same session in patients with pancreatic cancer.

Methods: Consecutive patients referred for EUS-FNA of a pancreatic mass with symptoms of biliary (±upper digestive) obstruction were included. Consecutive patients undergoing biliary and/or duodenal stenting without EUS-FNA during the same period were used as controls. Procedure-related complications were the primary outcome measure. Duration of the procedure, ability to achieve biliary/duodenal stenting, the yield of EUS-FNA, and clinical outcomes were evaluated.

Results: A total of 122 patients underwent combined EUS-FNA and stenting and 68 underwent stenting alone (control group). In the combined group, histological proof of cancer was obtained in 88.52% at first EUS-FNA and 95.08% after a second EUS-FNA. Biliary stent placement was successful in 97.5 and 98% in the combined and the control groups, respectively. There was no statistical difference between the groups for length of stay after endoscopy and for procedure-related mortality and morbidity within 30 days. The median time from endoscopy to chemotherapy in the combined group was 12 days.

Conclusion: Combined EUS-FNA and biliary and/or duodenal stenting is feasible in almost all patients with suspected pancreatic cancer, with no additional hazard and a high histological yield.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEG.0b013e328357cdfdDOI Listing
November 2012

Neoadjuvant sorafenib combined with gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma.

World J Gastroenterol 2011 May;17(17):2255-8

Department of Gastroenterology, Europeen Georges Pompidou Hospital, Medical University, 75908 Paris, France.

This paper reports the first case of a patient with hepatocellular carcinoma with lymph node metastasis treated by sorafenib combined with gemcitabine plus oxaliplatin, with a partial response and normalization of α fetoprotein, which allowed curative surgery. The potential synergy between these three drugs needs to be confirmed, and is currently being investigated in a randomized phase II trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v17.i17.2255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092880PMC
May 2011

Medical treatment of pancreatic cancer: new hopes after 10 years of gemcitabine.

Clin Res Hepatol Gastroenterol 2011 May 23;35(5):364-74. Epub 2011 Mar 23.

Service d'oncologie digestive, hôpital européen Georges-Pompidou, AP-HP, université Paris V, 20, rue Leblanc, 75015 Paris, France.

Exocrine pancreatic cancer has a very poor prognosis. R0 resection of the tumor is to date the only potentially curative approach, but less than 20% of patients are eligible for a curative surgery at diagnosis. Until recently, gemcitabine was the standard treatment for advanced and metastatic pancreatic cancer patients, since it was shown more than a decade ago to induce clinical benefit and to improve survival when compared to weekly bolus 5-fluorouracil. In order to improve patients' outcome many trials have, during the last 10 years, explored the pharmacokinetic modulation of gemcitabine and combination therapies with gemcitabine and other anti-cancer agents with consistent negative results. It is finally a trial assessing the efficacy of a combination chemotherapy without gemcitabine: the FOLFIRINOX regimen, reported this year, that has shown for the first time a significant improvement in progression free and overall survivals. In parallel, many trials testing new targeted agents in these patients are currently ongoing. After 10 years without significant progress in the treatment of pancreatic cancer patients, the hope that a significant improvement in the outcome of these patients can be achieved has been raised.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2011.02.002DOI Listing
May 2011