Publications by authors named "Marie-Pierre Galais"

23 Publications

  • Page 1 of 1

Sorafenib Plus Irinotecan Combination in Patients With RAS-mutated Metastatic Colorectal Cancer Refractory To Standard Combined Chemotherapies: A Multicenter, Randomized Phase 2 Trial (NEXIRI-2/PRODIGE 27).

Clin Colorectal Cancer 2020 Dec 15;19(4):301-310.e1. Epub 2020 May 15.

Medical Oncology Departement, Institut du Cancer de Montpellier (ICM), Univ. Montpellier, Montpellier, France; Institut régional du Cancer de Montpellier (IRCM), INSERM, Univ. Montpellier, ICM, Montpellier.

Background: No treatment option was available for patients with RAS-mutated (RASmt) metastatic colorectal cancer (mCRC) who progress after standard combined chemotherapies at the time of the study. After promising results in phase II, the aim of the present NEXIRI-2/PRODIGE 27 trial was to assess the 2-month non-progression rate for sorafenib (NEX) plus irinotecan (IRI), that is, NEXIRI, treatment.

Methods: Patients with RASmt mCRC after failure of oxaliplatin, IRI, fluoropyrimidines, and bevacizumab were randomized between NEXIRI (IRI 120-180 mg/m intravenous, D1 = D15 plus oral NEX 400 mg twice a day) versus IRI (180 mg/m) versus NEX. Primary endpoint was the 2-month non-progression rate. Secondary endpoints included progression-free and overall survival (PFS and OS), safety, and germline cyclin D1 (CCND1) rs9344 polymorphisms analyses.

Results: A total of 173 patients were included, 59 in NEXIRI, 57 in IRI, and 57 in NEX arms. The 2-month non-progression rate was 52.6% (95% confidence interval [CI]: 39%-66%), 21.4% (10%-33%), and 19.3% (9%-30%) for NEXIRI, IRI, and NEX. Median PFS was 3.6 (95% CI: 2-4.2), 1.7 (1.7-1.8), and 2 (1.8-2.3) months and the median OS was 7.2 (5.8-9.4), 6.3 (4.8-8), and 5.6 (3.9-7.7) months for NEXIRI, IRI, and NEX, respectively. For NEXIRI rs9344CCND1 A/A genotype patients, OS was 19.6 months (95% CI: 4.8-not reached). Main grade 3 toxicities included neutropenia, febrile neutropenia, diarrhea, hand-foot syndrome, and hypertension.

Conclusions: In patients with RASmt mCRC who progressed after standard combined chemotherapies, the results of 2-month non-progression rate and median PFS in the NEXIRI arm were in favor of an increase of the time before progression.
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http://dx.doi.org/10.1016/j.clcc.2020.04.008DOI Listing
December 2020

HYPHYCA: a prospective study in 613 patients conducting a comprehensive analysis for predictive factors of physiological F-FDG anal uptake.

EJNMMI Res 2020 Mar 20;10(1):28. Epub 2020 Mar 20.

INSERM 1086 ANTICIPE, Normandie University, Caen, France.

Background: Anal cancer is a relatively rare tumor of which incidence increases in developed countries. F-FDG PET has been increasingly used for its post radio-chemotherapy evaluation. However, several authors have reported the risk of local false-positive findings leading to low specificity and positive predictive values. These false-positive results could be due to post-radiotherapy inflammation or infection but certainly also to physiological anal canal uptake that is observed on a regular basis in clinical practice. The purpose of this prospective study (NCT03506529; HYPHYCA) was therefore to seek predictive factors of physiological anal canal hypermetabolism.

Materials And Methods: Over a 2-month period, patients aged 18 years old and more, referred for F-FDG PET-CT at two EARL-accredited PET centers were included, after obtaining their informed and written consent. They were asked to fill in a questionnaire including seven closed questions about usual intestinal transit, ongoing medications relative to intestinal transit, history of digestive, and anal and/or pelvic diseases. Age, gender, and body mass index (BMI) were recorded. A single nuclear medicine physician visually and quantitatively analyzed anal canal uptake (SUV) and assessed visual rectal content (air, feces, or both) and the largest rectal diameter (mm).

Results: Six hundred and thirteen patients were included (sex ratio F/M = 0.99) and 545 (89%) questionnaires were entirely completed. Significantly more males presented anal canal hypermetabolism (sex ratio (M/F) = 1.18 versus 0.85, p = 0.048). Moreover, patients with anal canal hypermetabolism had higher BMI (27.6 (5.7) kg/m versus 23.9 (4.5) kg/m, p < 0.0001), higher rate of hemorrhoid history (43% versus 27%, p = 0.016), and higher rate of rectum filled with only feces (21% versus 12%, p = 0.019) as compared to patients with no anal canal uptake. On logistic regression, all these variables were found to be independent predictors of the occurrence of an anal canal hypermetabolism. Odds ratio were 1.16 (1.12-1.20) per unit of BMI (kg/m) (p < 0.0001), 1.48 (1.04-2.11) for males (p = 0.030), 1.64 (1.10-2.45) for hemorrhoids history (p = 0.016), and 1.94 (1.147-3.22) for the rectum filled with only feces (p = 0.010).

Conclusion: According to our study, the predictive factors of physiological anal canal hypermetabolism are high BMI, male gender, hemorrhoid history, and rectum filled with only feces. This may pave the way to a more specific interpretation of post radio-chemotherapy PET evaluations of anal canal cancer, provided that other studies are conducted in this specific population.

Trial Registration: This prospective study was registered at Clinicaltrial.gov: NCT03506529; HYPHYCA on April 24, 2018.
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http://dx.doi.org/10.1186/s13550-020-0615-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082447PMC
March 2020

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

Implantation of tissue expander prior to irradiation in the era of intensity modulated radiotherapy: impact on the management of patients with pelvic digestive cancers.

Int J Colorectal Dis 2020 Mar 18;35(3):559-564. Epub 2019 Dec 18.

Centre François Baclesse, Radiation oncology Department, 3 avenue du general Harris, 14000, Caen, France.

Purpose: Before the introduction of intensity-modulated radiation therapy (IMRT), few teams used to implant a pelvic tissue expander to keep the bowel away from the radiation field, so as to reduce the risk of acute and late enteritis. However, this unexpected surgery could impact patient's overall treatment and may be no more necessary in the era of modern radiotherapy.

Material And Methods: This is a retrospective cross-sectional study including 13 patients who underwent tissue expander implantation before radiotherapy or chemoradiotherapy for rectal or anal carcinoma between November 2008 and March 2019. First, we aim to show that IMRT could sometimes be insufficient to respect dosimetric constraints, and then we aim to report the impact of tissue expander implantation on the global strategy of care of patients with anal and rectal cancers.

Results: Seventy-seven percent of the included patients were treated for anal neoplasms, while the remaining 23% had locally advanced rectal cancer. The median follow-up since implantation of the expander was 51 months [3.7-115]. Three patients recurred. One patient developed grade III toxicity related to the implantation of a tissue expander. The delay between diagnosis and the start of irradiation was significantly prolonged (median of 3 months), requiring unusual induction chemotherapy.

Conclusion: Implantation of tissue expander prior to chemoradiotherapy should be considered, even in the era of IMRT, when irradiated peritoneal cavity volume (V15Gy-V45Gy) far exceeds usual dose constraints. However, it impacts the global strategy of care by delaying the start of irradiation, by introducing induction chemotherapy, and rarely by causing post-operative complications.
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http://dx.doi.org/10.1007/s00384-019-03475-zDOI Listing
March 2020

Optimisation of chemotherapy prescription and preparation in an ambulatory unit: Validation of the OPTIMA program.

Eur J Cancer Care (Engl) 2019 May 20;28(3):e13015. Epub 2019 Feb 20.

Ambulatory Department, Centre François Baclesse, Caen, France.

Objective: We implemented the two-step OPTIMA program to anticipate chemotherapy prescription which aims to assess the discrepancy rate between anticipated and real prescription and its impact on waiting time and quality of care.

Methods: This prospective study included cancer patients receiving any intravenous chemotherapy. The OPTIMA program consists in a nurse phone call and a blood sample two days before the planned treatment. Collected information and biological results were used by a physician to issue a non-effective (step 1) or effective (step 2) anticipated prescription the day before the consultation. The real prescription was given as usual by another physician on the day of the consultation. Waiting time was collected, and patients' satisfaction with care was assessed with the OUT-PATSAT35 questionnaire.

Results: Respectively, 540 and 979 consultations (283 and 294 patients) were analysed in both steps. The discrepancy rate was 8.7% (step 1). In routine practice, the OPTIMA program (step 2) reduced patients' waiting time (median time 55 vs. 95 min, p < 0.001). A high general care satisfaction score was observed in both steps (80.7% and 80.2%).

Conclusions: This anticipation program demonstrated the accuracy of chemotherapy prescription, whatever the regimen and cancer site, and its impact on waiting time optimisation.
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http://dx.doi.org/10.1111/ecc.13015DOI Listing
May 2019

CA19.9 decrease >15% is a predictor of favourable outcome in patients treated for advanced pancreatic carcinoma: analysis of two independent cohorts.

HPB (Oxford) 2019 05 20;21(5):582-588. Epub 2018 Nov 20.

Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Digestive Oncology Unit and Department of Medical Oncology, Henri Becquerel Centre, Rouen, F 76000, Rouen, France. Electronic address:

Background: Although carbohydrate antigen 19.9 (CA19.9) is widely used in pancreatic adenocarcinoma (PA), no consensual cut-off value of CA19.9 decrease has been established for treatment monitoring.

Methods: This was a retrospective study including patients with a baseline CA19.9 ≥ 37 UI/ml and with locally advanced or metastatic PA from two French centers. CA19.9 measurements were performed at baseline and first CT-scan evaluation. The aim was to use a training set to determine the best cut-off of CA19.9 decrease for predicting progressive disease (PD) and to analyze its performance in an independent validation cohort.

Results: A total of 95 and 93 patients were included in the training and validation sets, respectively. A ≤15% CA19.9 decrease was the best cut-off for predicting PD with a sensitivity (Se) = 68% and a specificity (Sp) = 90%. In the validation set, this threshold was associated with Se = 76% and Sp = 83%. A >15% CA19.9 decrease was significantly associated with improved PFS (median 8.3 versus 3.1 months, p < 0.0001) and OS (median 14 versus 7.2 months, p < 0.0001). A >15% CA19.9 decrease was also identified as a factor independently associated with OS (HRa = 0.25, 95% CI:0.14-0.44).

Conclusions: A CA 19.9 decrease >15% is a favourable predictor of outcome in patients treated for advanced PA.
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http://dx.doi.org/10.1016/j.hpb.2018.09.006DOI Listing
May 2019

Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial.

J Clin Oncol 2018 05 5;36(15):1469-1477. Epub 2018 Apr 5.

Thierry André and Benoist Chibaudel, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris; Thierry André, Sorbonne Universités, UMPC Paris 06; Marine Hug de Larauze and Benoist Chibaudel and Thierry André, Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR); Christophe Louvet, Institut Mutualiste Montsouris; Céline Lepère, Hôpital Européen Georges Pompidou (HEGP); Gaël Deplanque, Groupe Hospitalier Saint-Joseph; Jean-Baptiste Bachet, Groupe Hospitalier Pitié Salpêtrière and Sorbonne Université, UMPC Paris 06; Ahmed Khalil, Hôpital Tenon; Julien Taieb, Hôpital Européen Georges Pompidou and Sorbonne Paris Cité, Université Paris Descartes, Paris; Julien Taieb, Fédération Française de Cancérologie Digestive; Jeremie Bez, Fédération Française de Cancérologie Digestive; François Ghiringhelli, Centre Georges-François Leclerc, Dijon; Dewi Vernerey and Sophie Paget-Bailly, CHU de Besançon; Serge Fratte, Hôpital de Besançon; Sophie Paget-Bailly, Franck Bonnetain and Dewi Vernerey INSERM UMR1098, Besançon; Laurent Mineur, Institut Sainte Catherine, Avignon; Jaafar Bennouna, Institut de Cancérologie de l'Ouest René Gauducheau, Saint-Herblain et Institut de Cancérologie Paul Papin, Angers; Jérôme Desrame, Hôpital Jean Mermoz, Lyon; Roger Faroux, Centre Hospitalier Départemental de La Roche sur Yon, La Roche sur Yon; Serge Fratte, Hôpital of Belfort-Montbeliard, Montbeliard; Jérôme Dauba, Centre Hospitalier Layné, Mont-de-Marsan; Olivier Dupuis, Clinique Victor Hugo, Le Mans; Yves Becouran, Institut Bergonié, Bordeaux; May Mabro, Hôpital Foch, Suresnes; Joëlle Egreteau, Centre Hospitalier de Bretagne Sud Site de Lorient, Lorient; Olivier Bouche, Hôpital Robert Debré, Reims; Marc Ychou, Institut du Cancer de Montpellier, and CHU de Montpellier, Montpellier; Marie Pierre Galais, Centre Francois Baclesse, Caen; Louis Marie Dourthe, Clinique Sainte Anne, Strasbourg; and Aimery de Gramont, Institut Hospitalier Franco-Britannique, Levallois-Perret, France.

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.
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http://dx.doi.org/10.1200/JCO.2017.76.0355DOI Listing
May 2018

In reply.

Semin Oncol 2017 04 4;44(2):161. Epub 2017 Aug 4.

Oncopharmacologie, ICO Paul Papin, Angers, France; Service d'Oncologie Médicale, ICO Paul Papin Angers, France; Service de Gastro-Entérologie, Centre Hospitalier Départemental Les Oudairies, La Roche sur Yon, France; Service d'Oncologie Médicale, CHU Jean Minjoz, Besançon, France; Service d'Oncologie et de Radiothérapie, Institut de Cancérologie et d'Hématologie, Brest, France; Service d'Oncologie Médicale, Centre François Baclesse, Caen, France; Service d'Hépatologie et de Gastroentérologie, Centre Hospitalier, Cholet, France; Service d'Oncologie Médicale, ICO René Gauducheau, Saint Herblain, France; Service d'Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire, Caen, France; Service d'Hépato-Gastro-Entérologie, Centre A. Lacassagne, Nice, France; Service d'Oncologie Médicale, Hôpital Henri Mondor, Creteil, France; Service d'Oncologie Médicale, Centre Hospitalier, Saumur, France; Service d'Onco-Hématologie, Centre Hospitalier, LeMans, France; Service d'Oncologie Médicale, Clinique Gentilly, Nancy, France; Service d'Hépato-Gastro-Entérologie, Proctologie et Oncologie Digestive 5B, Centre Hospitalier, Laval, France; Unité d'Hépato-Gastro-Entérologie,Centre Hospitalier Sartheet Loir, LaFleche, France; Service d'Hépato-Gastro-Entérologie, CHU Hôpital Trousseau, Tours, France; Centre Evaluation Clinique, ICO Paul Papin, Angers, France.

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http://dx.doi.org/10.1053/j.seminoncol.2017.08.002DOI Listing
April 2017

Prevention of 5-fluorouracil-induced early severe toxicity by pre-therapeutic dihydropyrimidine dehydrogenase deficiency screening: Assessment of a multiparametric approach.

Semin Oncol 2017 Feb 11;44(1):13-23. Epub 2017 Feb 11.

Oncopharmacologie, ICO Paul Papin, Angers, France.

5-Fluorouracil (5-FU)-based treatments can lead to early-onset severe (4%-5%) even fatal (0.3%) toxicities in patients with dihydropyrimidine dehydrogenase (DPD) deficiency. This multicenter prospective cohort study aimed to assess the clinical benefit of pretherapeutic screening for DPD deficiency using a multiparametric approach. Two parallel cohorts of patients treated with 5-FU-based chemotherapy for colorectal carcinoma were compared in a prospective nonrandomized study. In arm A, patients had DPD deficiency screening before treatment, whereas in arm B no pretherapy screening was performed. Dosing was based on 5-FU administration guidelines of each institution. DPD deficiency screening was performed using a combined multiparametric approach (5-FU). The frequency of early grade 4-5 toxic events potentially induced by 5-FU was compared in the two groups. At total of 1,142 patients (n = 1,116 evaluable) were enrolled. In arm A, out of 718 evaluable patients, nine grade 4 early toxicities potentially related to 5-FU were reported in nine patients (1.2%) with no toxic death despite one complete DPD deficiency and 24 partial deficiencies. The 24 patients with partial deficiency had safe pharmacokinetics (PK)-monitored 5-FU. In arm B, among 398 evaluable patients, 17 grade 4-5 toxic early events potentially related to 5-FU were reported in 12 patients (4.2%). The incidence of early severe toxicity was significantly higher in arm B (P = .0019), confirming the positive impact of pretherapeutic DPD assessment. The percent of patients with a toxicity grade 3 or higher observed in arm A was 10.8% (n = 78) compared to 17.55% (n = 69)  in arm B (P = .0497). The percentage of death was reduced from 2.5/1,000 in arm B to 0 in arm A. The time to occurrence of all grade ≥3 toxicities was determined in both arms and the difference between the two arms was significant (P = .047). Overall, one patient with complete DPD deficiency confirmed retrospectively died within 13 days from grade 5 multivisceral toxicity. Enrollment was prematurely closed after external experts' decision. In conclusion, multiparametric pretherapeutic DPD deficiency screening significantly lowered the risk of early severe toxicity and avoided an early toxic death. This approach should be used for safe administration of 5-FU-based treatments.
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http://dx.doi.org/10.1053/j.seminoncol.2017.02.008DOI Listing
February 2017

Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab.

Br J Clin Pharmacol 2017 03 24;83(3):623-631. Epub 2016 Oct 24.

Medical Oncology Department, Centre François Baclesse, Caen, France.

Aim: Cetuximab is an anti-epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab.

Methods: We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out at nine French centres. Pretreatment anti-cetuximab IgE levels were measured. We compared the proportion of severe HSRs in the low anti-cetuximab IgE levels (≤29 IgE arbitrary units) subgroup with that in a historical cohort of 213 patients extracted from a previous study.

Results: Of the 301 assessable patients (mean age: 60.9 ± 9.3 years, head-and-neck cancer: 77%), 66 patients (22%) had high anti-cetuximab IgE levels, and 247 patients received cetuximab (including 38 with high anti-cetuximab levels). Severe HSRs occurred in eight patients (five grade 3 and three grade 4). The proportion of severe HSRs was lower in the low anti-cetuximab IgE levels subgroup vs. the historical cohort (3/209 [1.4%] vs. 11/213 [5.2%], odds ratio, 0.27, 95% confidence interval, 0.07-0.97), and higher in high vs. low anti-cetuximab IgE levels subgroup (5/38 [13.2%] vs. 3/209 [1.4%]; odds ratio, 10.4, 95% confidence interval, 2.4-45.6). Patients with severe HSRs had higher anti-cetuximab IgE levels than patients without reaction (median, 45 vs. 2 IgE arbitrary units, P = 0.006).

Conclusions: Detection of pretreatment anti-cetuximab IgE is feasible and helpful to identify patients at risk of severe cetuximab-induced HSRs.
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http://dx.doi.org/10.1111/bcp.13140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306475PMC
March 2017

Chemoradiotherapy with FOLFOX plus cetuximab in locally advanced oesophageal cancer: The GERCOR phase II trial ERaFOX.

Eur J Cancer 2016 Mar 2;56:115-121. Epub 2016 Feb 2.

Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR), Paris, France; Medical Oncology Department, Saint-Antoine Universitary Hospital, Paris, France.

Background: To determine efficacy and toxicity of radiation therapy combined with oxaliplatin, 5-fluorouracil, and folinic acid (FOLFOX) and cetuximab in patients with locally advanced oesophageal cancer.

Patients And Methods: Patients with stage III oesophageal or gastro-oesophageal junction cancer were enrolled in a Simon's two-stage phase II study. Patients received FOLFOX and weekly cetuximab on week 1-10 with concurrent radiotherapy (50.4 Gy in 30 fractions) on week 5-10. Primary end-point was clinical overall response rate (ORR). An ORR rate of more than 50% was expected.

Results: Among the 79 included patients, clinical ORR was 77% with 40% complete responses. Median overall survival and progression-free survival were 21.6 and 11.3 months, respectively. The most common grade III-IV toxicities observed during experimental chemoimmunotherapy followed by chemoradiation included neutropenia (28%), oesophagitis (12%), rash (11%), and allergy (9%). There was one treatment-related death due to oesophagitis with gastrointestinal bleeding.

Conclusions: Cetuximab-FOLFOX regimen combined with radiotherapy demonstrated its efficacy and was well tolerated. Unfortunately, these results were not confirmed in two recent phase III studies.
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http://dx.doi.org/10.1016/j.ejca.2015.12.020DOI Listing
March 2016

First-Line Chemotherapy for Metastatic Esophageal Squamous Cell Carcinoma: Clinico-Biological Predictors of Disease Control.

Oncology 2016 20;90(2):88-96. Epub 2016 Jan 20.

Centre Oscar Lambret, Lille, France.

Objective: This study aimed to identify predictors of tumor control (TC) in metastatic esophageal squamous cell carcinoma patients receiving first-line chemotherapy.

Methods: A development cohort of 68 patients from a prospective multicenter trial (NCT01248299) was used to identify predictors of TC at first radiological tumor assessment and to generate a predictive score for TC. That score was applied in an independent retrospective single-center validation cohort of 60 consecutive patients.

Results: Multivariate analysis identified three predictors of TC: body mass index ≥18.5 (OR 4.5, 95% CI 0.91-22.5), absence of bone metastasis (OR 4.6, 95% CI 0.91-23.2) and albumin ≥35 g/l (OR 3.5, 95% CI 1.0-12.1). Based on the presence or absence of these three independent prognosticators, we built a predictive model using a score from 0 to 3. In the development cohort, the TC rates were 14.3 and 78.0% and in the validation cohort 12.5 and 44.2%, for scores of 0-1 and 2-3, respectively. With negative predictive values of 85 and 88% in the development and validation cohorts, respectively, we were able to identify patients with a very low probability of TC.

Conclusion: We have developed and validated a score that can be easily determined at the bedside to predict TC in metastatic esophageal squamous cell carcinoma patients.
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http://dx.doi.org/10.1159/000442947DOI Listing
June 2016

Asparagine Synthetase Expression and Phase I Study With L-Asparaginase Encapsulated in Red Blood Cells in Patients With Pancreatic Adenocarcinoma.

Pancreas 2015 Oct;44(7):1141-7

From the *Department of Hepato-Gastroenterology, Pitié Salpêtrière Hospital, Paris; and †Erytech Pharma, Lyon, France; ‡Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium; §Department of Oncology, Centre François Baclesse, Caen; ∥Department of Oncology, Centre Oscar Lambret, Lille; and ¶Pathology Department, Beaujon Hospital, Paris, France; #Department of Pathology, Erasme Hospital, Brussels, Belgium; **Department of Pathology, Saint Antoine Hospital; and ††Department of Pathology, Pitié Salpêtrière Hospital, Paris; ‡‡Department of Pathology, Ambroise Paré Hospital, Boulogne-Billancourt; and §§Department of Gastroenterology, Beaujon Hospital; and Departments of ∥∥Medical Oncology and ¶¶Oncology, Saint-Antoine Hospital, Paris, France.

Objectives: Asparaginase encapsulated in erythrocytes (ERY-ASP) is a potentially effective drug in patients with pancreatic adenocarcinoma (PAC) with null/low asparagine synthetase (ASNS) expression. Our aims were to assess ASNS expression in PAC from a large cohort and its prognostic and/or predictive value and to conduct a phase I trial with ERY-ASP in patients with metastatic PAC.

Methods: Asparagine synthetase expression was evaluated using immunohistochemistry in resected PAC (471 patients) and in pairs of primary tumor and metastases (55 patients). Twelve patients were included in the phase I trial and received a single administration of ERY-ASP (25-150 IU/kg).

Results: Null/low ASNS expression was found in 79.4% of the resected PAC with a high concordance between primary tumor and metastases. Asparagine synthetase expression was significantly correlated with sex and CXCR4 expression. In the phase I trial, ERY-ASP was well tolerated by patients with metastatic PAC. No patient had DLTs, and 6 patients had at least 1 ERY-ASP causally related adverse event out of the 12 adverse events reported.

Conclusions: Given the high rate of PAC with null/low ASNS expression and the good tolerability profile of ERY-ASP, ERY-ASP should be evaluated in further clinical studies in metastatic PAC.
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http://dx.doi.org/10.1097/MPA.0000000000000394DOI Listing
October 2015

How to improve the prevention of chemotherapy-induced nausea and vomiting? The French NAVI study.

Support Care Cancer 2016 Mar 14;24(3):1131-8. Epub 2015 Aug 14.

Centre François Baclesse, Clinical Research Department, av général Harris, Caen, 14000, France.

Purpose: Chemotherapy-induced nausea and vomiting (CINV) still remain frequent. The procedure for announcing the diagnosis (PAD) was an emblematic measure of the first French Plan Cancer aiming at providing patients with time to listen, information after cancer diagnosis, and discussion on treatments and their side effects. We aimed at assessing the risk factors of CINV, focusing on patients' satisfaction with the PAD.

Methods: This prospective multicentre study assessed the frequency and intensity of CINV among chemonaïve patients during the first cycle of treatment. CINV was defined by ≥1 emetic episode or reported nausea intensity ≥3 on a 0-10 scale. Multivariate analysis was used to identify factors related to global CINV onset including satisfaction with the PAD (satisfaction score ≥the median on a 0-10 scale).

Results: Data from 291 patients (women, 85.2%; mean age, 57 years) were analyzed. Most patients (69.4%) received highly emetogenic chemotherapy regimens and 77.7% received antiemetic drugs consistent with international guidelines. Acute, delayed and overall CINV were experienced by 40.4, 34.8 and 52.4% of patients, respectively. Sixty-seven per cent of patients were satisfied with the PAD. No relation was noted between PAD satisfaction and CINV onset. The nausea and vomiting dimension of the QLQ-C30 questionnaire before chemotherapy (OR 3.62), motion sickness history (OR 2.73), highly emetogenic CT (OR 2.73), anxiety (OR 1.99) and younger age (OR 1.96) were independent predictive factors.

Conclusions: Although patients were mostly satisfied with the PAD, half of them experienced CINV. A state of anxiety could be identified during the PAD to be managed.
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http://dx.doi.org/10.1007/s00520-015-2882-7DOI Listing
March 2016

Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset.

Authors:
Josef Thaler Richard Greil Johannes Gaenzer Wolfgang Eisterer Joerg Tschmelitsch Hellmut Samonigg August Zabernigg Franz Schmid Günther Steger Robert Steinacher Johannes Andel Alois Lang Reinhold Függer Friedrich Hofbauer Ewald Woell Dietmar Geissler Alfred Lenauer Manfred Prager Jean-Luc Van Laethem Eric Van Cutsem Geert D'Haens Gauthier Demolin Joseph Kerger Guido Deboever Gilbert Ghillebert Marc Polus Eric Van Cutsem Hassan RezaieKalantari Thierry Delaunoit Jean Charles Goeminne Marc Peeters Philippe Vergauwe Ghislain Houbiers Yves Humblet Jos Janssens Dirk Schrijvers Erik Vanderstraeten Jean-Luc Van Laethem Jan Vermorken Daniel Van Daele Michel Ferrante Frederic Forget Alain Hendlisz Mette Yilmaz Svend Erik Nielsen Lene Vestermark Jim Larsen Marc Ychou Ayman Zawadi Mohamed-Ayman Zawadi Olivier Bouche Laurent Mineur Jaafar Bennouna-Louridi Louis Marie Dourthe Marc Ychou Eveline Boucher Julien Taieb Denis Pezet Francoise Desseigne Michel Ducreux Patrick Texereau Laurent Miglianico Philippe Rougier Serge Fratte Charles-Briac Levache Yacine Merrouche Stephen Ellis Christophe Locher Jean-Francois Ramee Claire Garnier Frederic Viret Bruno Chauffert Isabelle Cojean-Zelek Pierre Michel Cedric Lecaille Christian Borel Jean-Francois Seitz Denis Smith Catherine Lombard-Bohas Thierry Andre Jean-Marc Gornet Francine Fein Marie-Aude Coulon-Sfairi Marie-Christine Kaminsky Jean-Paul Lagasse Dominique Luet Pierre-Luc Etienne Mohamed Gasmi Andre Vanoli Suzanne Nguyen Thomas Aparicio Hervé Perrier Noel Stremsdoerfer Philippe Laplaige Dominique Arsene Dominique Auby Laurent Bedenne Romain Coriat Bernard Denis Patrick Geoffroy Gilles Piot Yves Becouarn Gilbert Bordes Gael Deplanque Olivier Dupuis Frederic Fruge Rosine Guimbaud Thierry Lecomte Gérard Lledo Iradej Sobhani Amani Asnacios Ahmed Azzedine Christophe Desauw Marie-Pierre Galais Dany Gargot You-Heng Lam Abakar Abakar-Mahamat Jean-Francois Berdah Sylviane Catteau Marie-Christine Clavero-Fabri Jean-Francois Codoul Jean-Louis Legoux Denis Goldfain Pierre Guichard Denis Pere Verge Jocelyne Provencal Bruno Vedrenne Catherine Brezault-Bonnet Denis Cleau Jean-Paul Desir David Fallik Bruno Garcia Marie-Hélène Gaspard Dominique Genet Johannes Hartwig Yves Krummel Tamara MatysiakBudnik Vanessa Palascak-Juif Harizo Randrianarivelo Yves Rinaldi Albert Aleba Ariane Darut-Jouve Aimery de Gramont Herve Hamon Frederic Wendehenne Axel Matzdorff Michael Konrad Stahl Wolfgang Schepp Martin Burk Lothar Mueller Gunnar Folprecht Michael Geissler Luisa Mantovani-Loeffler Thomas Hoehler Walter Asperger Hendrik Kroening Ludwig Fischer von Weikersthal Stefan Fuxius Matthias Groschek Johannes Meiler Tanja Trarbach Jacqueline Rauh Nicolas Ziegenhagen Albrecht Kretzschmar Ullrich Graeven Arnd Nusch Goetz von Wichert Ralf-Dieter Hofheinz Gerhard Kleber Karl-Heinz Schmidt Ursula Vehling-Kaiser Claudia Baum Jochen Schuette Georg Martin Haag Wilhelm Holtkamp Jochen Potenberg Tobias Reiber Georg Schliesser Hans-Joachim Schmoll Wolfgang Schneider-Kappus Wolfgang Abenhardt Claudio Denzlinger Jan Henning Bartscht Marxsen Hans GuenterDerigs Helmut Lambertz Ingulf Becker-Boost Karel Caca Christian Constantin Thomas Decker Henning Eschenburg Sigrun Gabius Holger Hebart Albrecht Hoffmeister Heinz-August Horst Stephan Kremers Malte Leithaeuser Sebastian Mueller Siegfried Wagner Severin Daum Frank Schlegel Martina Stauch Volker Heinemann Roberto Labianca Giuseppe Colucci Dino Amadori Enrico Mini Alfredo Falcone Corrado Boni Evaristo Maiello Luciano Latini Alberto Zaniboni Dino Amadori Giuseppe Aprile Sandro Barni Rodolfo Mattioli Andrea Martoni Rodolfo Passalacqua Mario Nicolini Enzo Pasquini Carla Rabbi Enrico Aitini Alberto Ravaioli Carlo Barone Guido Biasco Stefano Tamberi Angelo Gambi Claudio Verusio Marina Marzola Giorgio Lelli Corrado Boni Stefano Cascinu Paolo Bidoli Massimo Vaghi Giorgio Cruciani Francesco Di Costanzo Alberto Sobrero Enrico Mini Roberto Petrioli Massimo Aglietta Oscar Alabiso Federico Capuzzo Alfredo Falcone Domenico Cristi Corsi Roberto Labianca Stefania Salvagni Silvana Chiara Francesco Ferraù Francesco Giuliani Sara Lonardi Nicola Gebbia Giovanni Mantovani Evaristo Sanches Evaristo Sanches Juan Carlos Mellidez Pedro Santos Joao Freire Cristina Sarmento Luis Costa Antonio Moreira Pinto Sergio Barroso Jorge Espirito Santo Fátima Guedes Amélia Monteiro Anabela Sa Irene Furtado Josep Tabernero Ramon Salazar Enrique Aranda Aguilar Fernando Rivera Herrero Josep Tabernero Javier Sastre Valera Manuel ValladaresAyerbes Jaime FeliuBatlle Silvia Gil Carlos Garcia-Giron Guillermo Lopez Vivanco Antonia Salud Salvia Vicente Alonso Orduña Ruth Vera Garcia Javier Gallego Bartomeu Massuti Sureda Jordi Remon Maria Jose Safont Aguilera Luis CireraNogueras BernadoQueralt Merino Cristina Gravalos Castro Purificacion Martinez de Prado Carlos PijaumePericay Manuel ConstenlaFigueiras InmaculadaGuasch Jordan Maria Jose GomeReina Amelia Lopez-Ladron Garcia Antonio Arrivi Garcia-Ramos Andres Cervantes Carlos Fernandez Martos Eugenio MarcuelloGaspar Ines Cabezas Montero Pilar Escudero Emperador Ana Leon Carbonero Manuel Gallen Castillo Teresa Garcia Garcia Jose Garcia Lopez Encarnacion Gonzalez Flores Monica GuillotMorales Marta LlanosMuñoz Ana López Martín Joan Maurel Juan Carlos Camara Rosario Dueñas Garcia Mercedes Salgado Isabel HernandezBusquier Teresa Checa Ruiz Adelaida LacastaMuñoa MiquelNogue Aliguer Amalia Velasco Ortiz de Taranco Miguel Mendez Ureña Ferran Losa Gaspa Jose Juan Ponce Carlos Bosch Roig Pedro Valero Jimenez Antonio GalanBrotons Santiago AlbiolRodriguez Jose Ales Martinez Liliana Canosa Ruiz Margarita CentellesRuiz John Bridgewater Rob Glynne-Jones Saad Tahir Tamas Hickish Jim Cassidy Leslie Samuel

Ann Oncol 2015 Apr;26(4):822-825

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http://dx.doi.org/10.1093/annonc/mdv070DOI Listing
April 2015

Risk factors associated with hypersensitivity reactions to cetuximab: anti-cetuximab IgE detection as screening test.

Future Oncol 2014 Nov;10(14):2133-40

Department of Hepato-Gastroenterology & Nutrition, Caen University Hospital, Avenue Côte de Nacre, CHU Côte de Nacre, 14033 Caen cedex 9, France.

Aim: To describe the factors associated with a high risk of a hypersensitivity reaction to cetuximab.

Patients & Methods: We retrospectively studied a cohort of patients living in Normandy (France) treated with cetuximab.

Results: Among the 229 treated patients, 24 (10.5%) had a hypersensitivity reaction to cetuximab, including 11 grade 3-5 reactions. Detection of anti-cetuximab IgE could be performed in 108 patients. Anti-cetuximab IgE was found in 13 of 17 patients (76.5%) who had a hypersensitivity reaction to cetuximab compared with 17 of 91 control patients (18.7%; adjusted odds ratio: 14.99; 95% CI: 3.59-62.63). No clinical criteria predicted the risk of allergy to cetuximab.

Conclusion: Anti-cetuximab IgE may help physicians identify patients at risk of a hypersensitivity reaction to cetuximab.
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http://dx.doi.org/10.2217/fon.14.153DOI Listing
November 2014

Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial.

Lancet Oncol 2014 Mar 18;15(3):305-14. Epub 2014 Feb 18.

Département de Cancérologie Digestive et Urologique, Centre Oscar Lambret, Lille, France.

Background: Definitive chemoradiotherapy is a curative treatment option for oesophageal carcinoma, especially in patients unsuitable for surgery. The PRODIGE5/ACCORD17 trial aimed to assess the efficacy and safety of the FOLFOX treatment regimen (fluorouracil plus leucovorin and oxaliplatin) versus fluorouracil and cisplatin as part of chemoradiotherapy in patients with localised oesophageal cancer.

Methods: We did a multicentre, randomised, open-label, parallel-group, phase 2/3 trial of patients aged 18 years or older enrolled from 24 centres in France between Oct 15, 2004, and Aug 25, 2011. Eligible participants had confirmed stage I-IVA oesophageal carcinoma (adenocarcinoma, squamous-cell, or adenosquamous), Eastern Cooperative Oncology Group (ECOG) status 0-2, sufficient caloric intake, adequate haematological, renal, and hepatic function, and had been selected to receive definitive chemoradiotherapy. Patients were randomly assigned (1:1) to receive either six cycles (three concomitant to radiotherapy) of oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), bolus fluorouracil 400 mg/m(2), and infusional fluorouracil 1600 mg/m(2) (FOLFOX) over 46 h, or four cycles (two concomitant to radiotherapy) of fluorouracil 1000 mg/m(2) per day for 4 days and cisplatin 75 mg/m(2) on day 1. Both groups also received 50 Gy radiotherapy in 25 fractions (five fractions per week). Random allocation to treatment groups was done by a central computerised randomisation procedure by minimisation, stratified by centre, histology, weight loss, and ECOG status, and was achieved independently from the study investigators. The primary endpoint was progression-free survival. Data analysis was primarily done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00861094.

Findings: 134 participants were randomly allocated to the FOLFOX group and 133 to the fluorouracil and cisplatin group (intention-to-treat population), and 131 patients in the FOLFOX group and 128 in the fluorouracil and cisplatin group actually received the study drugs (safety population). Median follow-up was 25·3 months (IQR 15·9-36·4). Median progression-free survival was 9·7 months (95% CI 8·1-14·5) in the FOLFOX group and 9·4 months (8·1-10·6) in the fluorouracil and cisplatin group (HR 0·93, 95% CI 0·70-1·24; p=0·64). One toxic death occurred in the FOLFOX group and six in the fluorouracil-cisplatin group (p=0·066). No significant differences were recorded in the rates of most frequent grade 3 or 4 adverse events between the treatment groups. Of all-grade adverse events that occurred in 5% or more of patients, paraesthesia (61 [47%] events in 131 patients in the FOLFOX group vs three [2%] in 128 patients in the cisplatin-fluorouracil group, p<0·0001), sensory neuropathy (24 [18%] vs one [1%], p<0·0001), increases in aspartate aminotransferase concentrations (14 [11%] vs two [2%], p=0·002), and increases in alanine aminotransferase concentrations (11 [8%] vs two [2%], p=0·012) were more common in the FOLFOX group, whereas serum creatinine increases (four [3%] vs 15 [12%], p=0·007), mucositis (35 [27%] vs 41 [32%], p=0·011), and alopecia (two [2%] vs 12 [9%], p=0·005) were more common in the fluorouracil and cisplatin group.

Interpretation: Although chemoradiotherapy with FOLFOX did not increase progression-free survival compared with chemoradiotherapy with fluorouracil and cisplatin, FOLFOX might be a more convenient option for patients with localised oesophageal cancer unsuitable for surgery.

Funding: UNICANCER, French Health Ministry, Sanofi-Aventis, and National League Against Cancer.
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http://dx.doi.org/10.1016/S1470-2045(14)70028-2DOI Listing
March 2014

Sorafenib increases 18-FDG colic uptake: demonstration in patients with differentiated thyroid cancer.

EJNMMI Res 2012 May 7;2(1):18. Epub 2012 May 7.

Departments of Nuclear Medicine and Thyroid Unit, Centre François Baclesse, 3 Avenue Général Harris - BP 5026, Cedex 05, Caen, 14076, France.

Background: To assess 18-fluorodeoxyglucose (FDG) bowel uptake in patients with differentiated thyroid cancer (DTC) treated with sorafenib.

Findings: Visual (5-point scale) and high maximum standard uptake value (SUVmax) semi-quantitative analyses were conducted in 63 positron emission tomography (PET) studies performed in patients on sorafenib (group 1, n = 20), in a control group (group 2, n = 28) and in patients on sunitinib or vandetanib (group 3, n = 15).Moderate or high and diffuse bowel uptake (grade 4 or 5) was observed in 90% of the PET scans of group 1 versus none in group 2. Only 20% of PET scans in group 3 were scored grade 4. SUVmax values were significantly higher for all colic segments in group 1 than in group 2 (P < 0.0001) or 3 (P < 0.0004). This uptake pattern appeared rapidly (one month) and disappeared after sorafenib withdrawal.

Conclusions: FDG uptake is increased in the colon of DTC patients treated by sorafenib.
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http://dx.doi.org/10.1186/2191-219X-2-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426461PMC
May 2012

Anti-cetuximab IgE ELISA for identification of patients at a high risk of cetuximab-induced anaphylaxis.

MAbs 2011 Jul-Aug;3(4):396-401. Epub 2011 Jul 1.

Laboratoire d'Immunologie et Immunopathologie, Centre Hospitalier Universitaire, Caen, France.

Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, has proven effective in the treatment of metastatic colorectal cancer and squamous cell carcinoma of the head and neck. However, a high incidence of immediate hypersensitivity reactions (HSR) to cetuximab after the first infusion has been observed. We have developed a test for identification of patients likely to show treatment-related HSR to cetuximab. An enzyme-linked immunosorbent assay (ELISA) for detecting anti-cetuximab IgEs was developed and tested on serum samples collected from cancer patients before start of cetuximab treatment, and from healthy blood donors. Similar levels of anti-cetuximab IgE were detected in pre-treatment patient sera (24/92, 26.1%) and sera from healthy blood donors (33/117, 28.2%). HSR were observed in 14 out of the 92 patients (15.2%), and 8 of these (57.1%) were grade 3-4. Anti-cetuximab IgEs were detected in 7/8 of the patients (87.5%) with severe HSRs as compared with 14/78 patients (17.9%) with no HSR (p=0.0002). Predictive value of the anti-cetuximab IgE test for HSR events of grades 3-4 was calculated using Receiver Operating Characteristics analysis. With a cut-off value of 29 arbitrary units for the anti-cetuximab IgE, the ELISA test showed a sensitivity of 87.5%, specificity of 82.1%, positive predictive value of 33.3% and negative predictive value of 98.5%. Anti-cetuximab IgE ELISA detection could be a valuable tool to help the physician anticipate an anaphylaxis episode following cetuximab infusion and opt for a suitable alternative treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218536PMC
http://dx.doi.org/10.4161/mabs.3.4.16293DOI Listing
January 2012

Recent developments in colorectal cancer treatment by monoclonal antibodies.

Expert Opin Biol Ther 2006 Nov;6(11):1175-92

Centre Hospitalier Universitaire de Caen, Service d'Hépato-Gastro-Entérologie et Nutrition, Avenue Côte de Nacre, 14033 Caen Cedex, France.

A growing understanding of the molecular mechanisms involved in cancer biology and continuous refinement of available technologies for drug discovery have prompted the development of new therapeutic tools targeting specific cancer-associated molecular pathways. Among these so-called biological therapies, monoclonal antibodies have now reached the time of clinical application. Besides initial development of the murine antibody edrecolomab, the impact of monoclonal antibodies on cancer therapy has recently been clearly demonstrated in colorectal cancer by targeting two major pathways critical to tumourigenesis: the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) signalling pathways. These antibodies showed significant clinical activity in advanced colorectal cancer, especially when combined with chemotherapy. This paper reviews the status of the monoclonal chimeric antibody cetuximab (Erbitux) and other anti-EGFR antibodies, and of bevacizumab (Avastin; an anti-VEGF humanised monoclonal antibody), in colorectal cancer treatment.
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http://dx.doi.org/10.1517/14712598.6.11.1175DOI Listing
November 2006

Impact of radiation schedule and chemotherapy duration in definitive chemoradiotherapy regimen for esophageal cancer.

Gastroenterol Clin Biol 2006 Jun-Jul;30(6-7):845-51

Digestive Oncology Unit, Hepatogastroenterology Department, Rouen University Hospital- Charles Nicolle, Rouen.

Unlabelled: Impact of radiotherapy (RT) schedule on local response and duration of the 5-fluorouracil/cisplatin (5 FU/CDDP) chemotherapy (CT) on m are still questioning in chemoradiotherapy (CRT) regimen in esophageal carcinoma.

Aim: Evaluate two RT schedules and two different CT durations by a retrospective comparison of the CRT regimens used by two centres between 1994 and 2000.

Methods: In centre I (regimen I), patients received 2 CT concomitantly to a continuous RT (50 Gy/25 fractions/5 weeks). In centre II (regimen II), patients received 6 CT, 3 were concomitant to a split course RT (20 Gy/10 fractions x 3 courses) and 3 CT were delivered after CRT.

Results: A total of 129 patients were included, 74 in centre I and 55 in centre II respectively. Main patient characteristics were similar between the two groups. Clinical complete response to CRT was significantly more frequent in regimen I (83.8% vs 65.4%; P=0.02). The median overall survival (OS) was 20 months in regimen I and 22 months in regimen II (NS). During follow-up, responder patients to CRT in regimen II experienced significant fewer metastasis (51.6% vs 27.8%; P=0.03) with a trend to an increased 5-year survival (19.4% vs 11.3%) and OS (26.5 vs 21.0 months) (NS). Grade 3-4 toxicities were not different.

Conclusion: Clinical complete response to CRT was significantly more frequent with a continuous RT whereas additional CT after CRT significantly reduced metastasis occurrence. CRT regimen in esophageal carcinoma may be more effective using a continuous RT schedule and additional CT courses after CRT completion.
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http://dx.doi.org/10.1016/s0399-8320(06)73331-0DOI Listing
October 2006

Predictive factors of survival in patients treated with definitive chemoradiotherapy for squamous cell esophageal carcinoma.

World J Gastroenterol 2006 Jul;12(26):4185-90

Digestive Oncology Unit, Hepatogastroenterology Department, Rouen University Hospital, France.

Aim: The aim of the study was to evaluate the predictive factors of survival in patients with locally advanced squamous cell esophageal carcinoma (LASCOC) treated with definitive chemoradiotherapy (CRT) regimen based on the 5FU/CDDP combination.

Methods: All patients with LASCOC treated with a definitive CRT using the 5FU/CDDP combination between 1994 and 2000 were retrospectively included. Clinical complete response (CCR) to CRT was assessed by esophageal endoscopy and CT-scan 2 mo after CRT completion. Prognostic factors of survival were assessed using univariate and multivariate analysis by the Cox regression model.

Results: A total of 116 patients were included in the study. A CCR to CRT was observed in 86/116 (74.1%). The median survival was 20 mo (range 2-114) and the 5-year survival was 9.4%. Median survival of responder patients to CRT was 25 mo (range 3-114) as compared to 9 mo (range 2-81) in non-responder patients (P < 0.001). In univariate analysis, survival was associated with CCR (P < 0.001), WHO performance status < 2 (P = 0.01), tumour length < 6 cm (P = 0.045) and weight loss < 10% was in limit of significance (P = 0.053). In multivariate analysis, survival was dependant to CCR (P < 0.0001), weight loss < 10% (P = 0.034) and WHO performance < 2 (P = 0.046).

Conclusion: Our results suggest that survival in patients with LASCOC treated with definitive CRT was correlated to CCR, weight loss and WHO performance status.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087370PMC
http://dx.doi.org/10.3748/wjg.v12.i26.4185DOI Listing
July 2006

[Hydration of patients treated with cisplatin: practical investigation and establishment of a protocol].

Therapie 2005 Sep-Oct;60(5):499-505

Pharmacie Centrale, CHU de Caen, Caen, France.

Background: Administration of cisplatin requires hyperhydration of the patient to prevent nephrotoxic effects of this molecule.

Materials And Methods: A survey done in different hospitals - university hospitals, general hospitals and cancer institutes--has shown a large variability in the hydration protocols. A multidisciplinary group was set up in our university hospital comprising oncologists, nephrologists and pharmacists. This group has developed a consensual local protocol from a bibliographic analysis (Medline) and from the personal experience of each member.

Conclusion: This protocol was approved by our hospital's Committee of Drugs and Medical Devices.
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http://dx.doi.org/10.2515/therapie:2005071DOI Listing
March 2006