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IF 7.191 (2017); International audience; BACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI more...

The clinical benefit of double-front-line therapy (including oxaliplatin or irinotecan or bevacizumab plus 5-fluorouracil (5FU) or capecitabine) compared to monotherapy (5FU or capecitabine) in elderly (> 70 years) patients with metastatic colorectal cancer (MCRC) is controversial. We performed a meta-analysis of published randomized studies. The selection of the studies was carried out using PubMed with the following keywords: “metastatic colorectal cancer,” “elderly,” “oxaliplatin,” “irinotecan,” “bevacizumab,” “survival.” The efficacy endpoints were overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) with their 95% confidence intervals (CIs) were collected from the studies and pooled. By convention, an HR more...

Background Patterns of disease recurrence in patients with oesophageal cancer following treatment with neoadjuvant chemoradiotherapy and surgery (nCRTS) or surgery alone are poorly reported. An understanding of patterns of disease recurrence is important for subsequent treatment planning. Methods An analysis was undertaken of patterns of disease recurrence from a phase III multicentre randomized trial (FFCD9901) comparing nCRTS with surgery alone in patients with stage I and II oesophageal cancer. Results Some 170 patients undergoing surgical resection were included in the study. R0 resection rates were similar in the two groups: 94 per cent following nCRTSversus 92 per cent after surgery alone (P = 0·749). After a median follow-up of 94·2 months, recurrent disease was found in 39·4 per cent of the overall cohort (31 per cent after nCRTSversus 47 per cent following surgery alone; P = 0·030). Locoregional recurrence was diagnosed in 41 patients (17 versus 30 per cent respectively; P = 0·047) and distant metastatic recurrence in 47 (23 versus 31 per cent respectively; P = 0·244). Metastatic recurrence was more frequent in patients with adenocarcinoma than in those with squamous cell cancer (40 versus 23·1 per cent respectively; P = 0·032). ypT0 N0 category was associated with prolonged time to mixed locoregional and metastatic recurrence (P = 0·009), and time to locoregional (P = 0·044) and metastatic (P = 0·055) recurrence. In multivariable analysis, node-positive disease predicted both locoregional (P = 0·001) and metastatic (P < 0·001) recurrence. Conclusion Locoregional disease control following nCRTS indicated a local field effect not related solely to completeness of resection. pN+ disease was strongly predictive of time to locoregional and metastatic disease recurrence. more...

Objective: The study objectives were to analyze the impact of the number of lymph nodes (LNs) reported as resected (NLNr) and the number of LNs invaded (NLNi) on the prognosis of esophageal cancer (EC) after neoadjuvant chemoradiotherapy. Background: Pathological LN status is a major disease prognostic factor and marker of surgical quality. The impact of neoadjuvant chemoradiation (nCRT) on LN status remains poorly studied in EC. Methods: Post hoc analysis from a phase III randomized controlled trial comparing nCRT and surgery (group nCRT) to surgery alone (group S) in stage I and II EC (NCT00047112). Only patients who underwent surgical resection were considered (n = 170). Results: nCRT resulted in tumoral downstaging (pT0, 40.7% vs 1.1%, P 3 vs 0) 3.5, 95% CI: 2.0-6.2, P = 15) 0.95, 95% CI: 0.6-1.4, P = 0.807 and HR ( = 23) 1.4, 95% CI: 0.9-2.0, P = 0.131] did not. In Poisson regression analysis, nCRT was an independent predictive variable for reduced NLNr [exp(coefficient) 0.80, 95% CI: 0.66-0.96, P = 0.018]. Conclusions: nCRT is not only responsible for disease downstaging but also predicts fewer LNs being identified after surgical resection for EC. This has implications for the current quality criteria for surgical resection more...

IF 3.061; International audience; Oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. Two recent retrospective studies strongly suggested that low-dose aspirin used (100 mg/d) after surgical resection of colorectal cancer with a PIK3CA mutation could act as a targeted therapy with a major protective effect on the risk of recurrence. We propose a double-blind randomized phase III study to evaluate aspirin (100 mg/d during 3 years or until recurrence) versus placebo. Main inclusion criteria are patients aged 18 or 20, stage III or high risk stage II. The primary endpoint of the study is 3-year disease-free survival (DFS). Hypotheses are to improve 3-years DFS from placebo: 72% to aspirin: 83% (HR = 0.56). 94 events and 264 patients with PIK3CA mutation are required. The secondary endpoints are DFS at 5 years, the overall survival rate at 5 years, grade 3-4 severe bleeding. more...

IF 4.328; International audience

Purpose To compare epirubicin, cisplatin, and capecitabine (ECX) with fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatments in patients with advanced gastric or esophagogastric junction (EGJ) adenocarcinoma. Patients and Methods This open, randomized, phase III study was carried out in 71 centers. Patients with locally advanced or metastatic gastric or EGJ cancer were randomly assigned to receive either ECX as first-line treatment (ECX arm) or FOLFIRI (FOLFIRI arm). Second-line treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). The primary criterion was time-to-treatment failure (TTF) of the first-line therapy. Secondary criteria were progression-free survival (PFS), overall survival (OS), toxicity, and quality of life. Results In all, 416 patients were included (median age, 61.4 years; 74% male). After a median follow-up of 31 months, median TTF was significantly longer with FOLFIRI than with ECX (5.1 v 4.2 months; P = .008). There was no significant difference between the two groups in median PFS (5.3 v 5.8 months; P = .96), median OS (9.5 v 9.7 months; P = .95), or response rate (39.2% v 37.8%). First-line FOLFIRI was better tolerated (overall rate of grade 3 to 4 toxicity, 69% v 84%; P < .001; hematologic adverse events [AEs], 38% v 64.5%; P < .001; nonhematologic AEs: 53% v 53.5%; P = .81). Conclusion FOLFIRI as first-line treatment for advanced gastric and EGJ cancer demonstrated significantly better TTF than did ECX. Other outcome results indicate that FOLFIRI is an acceptable first-line regimen in this setting and should be explored as a backbone regimen for targeted agents. more...

Purpose Although often investigated in locally advanced esophageal cancer (EC), the impact of neoadjuvant chemoradiotherapy (NCRT) in early stages is unknown. The aim of this multicenter randomized phase III trial was to assess whether NCRT improves outcomes for patients with stage I or II EC. Methods The primary end point was overall survival. Secondary end points were disease-free survival, postoperative morbidity, in-hospital mortality, R0 resection rate, and prognostic factor identification. From June 2000 to June 2009, 195 patients in 30 centers were randomly assigned to surgery alone (group S; n = 97) or NCRT followed by surgery (group CRT; n = 98). CRT protocol was 45 Gy in 25 fractions over 5 weeks with two courses of concomitant chemotherapy composed of fluorouracil 800 mg/m2 and cisplatin 75 mg/m2. We report the long-term results of the final analysis, after a median follow-up of 93.6 months. Results Pretreatment disease was stage I in 19.0%, IIA in 53.3%, and IIB in 27.7% of patients. For group CRT compared with group S, R0 resection rate was 93.8% versus 92.1% (P = .749), with 3-year overall survival rate of 47.5% versus 53.0% (hazard ratio [HR], 0.99; 95% CI, 0.69 to 1.40; P = .94) and postoperative mortality rate of 11.1% versus 3.4% (P = .049), respectively. Because interim analysis of the primary end point revealed an improbability of demonstrating the superiority of either treatment arm (HR, 1.09; 95% CI, 0.75 to 1.59; P = .66), the trial was stopped for anticipated futility. Conclusion Compared with surgery alone, NCRT with cisplatin plus fluorouracil does not improve R0 resection rate or survival but enhances postoperative mortality in patients with stage I or II EC. more...

IF 6.163; International audience; AIM:Several predictors of metastatic colorectal cancer (mCRC) outcomes have been described. Specific geriatric characteristics could be of interest to determine prognosis.METHOD:Elderly patients (75+) with previously untreated mCRC were randomly assigned to receive infusional 5-fluorouracil-based chemotherapy, either alone (FU) or in combination with irinotecan (IRI). Geriatric evaluations were included as an optional procedure. The predictive value of geriatric parameters was determined for the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).RESULTS:From June 2003 to May 2010, the FFCD 2001-02 randomised trial enrolled 282 patients. A baseline geriatric evaluation was done in 123 patients; 62 allocated to the FU arm and 61 to the IRI arm. The baseline Charlson index was ≤1 in 75%, Mini-Mental State Examination was ≤27/30 in 31%, Geriatric Depression Scale was >2 in 10% and Instrumental Activities of Daily Living (IADL) was impaired in 34% of the patients. Multivariate analyses revealed that no geriatric parameter was predictive for ORR or PFS. Normal IADL was independently associated with better OS. The benefit of doublet chemotherapy on PFS differed in subgroups of patients ≤80 years, with unresected primary tumour, leucocytes >11,000 mm3 and carcinoembryonic antigen >2N. There was a trend towards better OS in patients with normal IADL.CONCLUSION:The autonomy score was an independent predictor for OS. A trend toward a better efficacy of doublet chemotherapy in some subgroups of patients was reported and should be further explored. more...

Purpose Controversy exists regarding whether or not amifostine might reduce the efficacy of cancer treatment. The aim of this meta-analysis was to evaluate the impact of amifostine on overall survival (OS) and progression-free survival (PFS) in patients treated with radiotherapy or chemoradiotherapy. Material and Methods Updated data from individual patients with non–small-cell lung cancer, head and neck squamous cell carcinoma, and pelvic cancer treated with radiotherapy or chemoradiotherapy and randomly assigned to amifostine or not were included. The primary end point was OS. Results Twenty-two randomized trials (2,279 patients) were potentially eligible. Data were available for 16 trials (1,554 patients), but four trials (435 patients) were excluded after data checking. Ultimately 12 trials and 1,119 patients were analyzed. A total of 431 patients were treated with radiotherapy alone (three trials), and 688 patients were treated with chemoradiotherapy (nine trials). Thirty-three percent of patients had lung cancers, 65% had head and neck cancers, and 2% had pelvic carcinomas. Ninety-one percent of patients had locally advanced disease (early stage, 9%). Median follow-up was 5.2 years. The hazard ratio (HR) of death was 0.98 (95% CI, 0.84 to 1.14; P = .78). On the basis of 11 trials (1,091 patients), the HR of progression, relapse, or death was 1.05 (95% CI, 0.90 to 1.22; P = .53). The tests for heterogeneity were not significant (P ≥ .73), and there was no significant variation of treatment effect according to sex, age, tumor site, stage, histology, locoregional treatment, or type of administration for either end point. Conclusion Amifostine did not reduce OS and PFS in patients treated with radiotherapy or chemoradiotherapy. more...

Background The Federation Francophone de Cancerologie Digestive phase III trial in patients with metastatic pancreatic adenocarcinoma comparing 5FU, folinic acid and cisplatin combination followed by gemcitabine (Arm A) versus the opposite sequence (Arm B) failed to demonstrate a benefit in overall survival. To longitudinally compare the quality of life (QoL) we explored different definitions of time until definitive deterioration (TUDD) of QoL scores according to minimal clinically important difference (MCID) cut-offs. Methods QoL was evaluated using the EORTC QLQ-C30 every 8 weeks until death. The following scores were analysed: global health, emotional functioning, physical functioning, fatigue and pain. TUDD was defined as the time interval between randomisation and the first occurrence of a decrease in QLQ-C30 score ⩾5 points without any further improvement in QoL score ⩾5 points or any further available QoL data. Analyses were repeated using a 10 point MCID and/or including death as event. Results From 08/2003 to 05/2006, 102 patients in Arm A and 100 in Arm B were included. Using a 5 and a 10 point MCID, TUDD curves of the 5 scores did not differ according to treatment arm., The median TUDD of global health was 5.2 months (4.3–6.2) in Arm A and 6.1 months (5.1–8.5) in Arm B (log-rank p = 0.50) including death as an event for a 5 point MCID. Multivariate Cox model showed that tumour localisation and progression were independently associated with TUDD (p Conclusions The strategy of chemotherapy did not influence the deterioration of QoL. The TUDD approach seems to provide meaningful clinical results that are adapted to metastatic pancreatic adenocarcinoma trials. more...

International audience; BACKGROUND:Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.PATIENTS AND METHODS:Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).RESULTS:From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%).CONCLUSION:In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.CLINICALTRIALSGOV:NCT00303771. more...

High-dose FOLFIRI has an acceptable safety profile and promising efficacy. UDP-glucuronosyltransferase: (UGT1A1) polymorphism may be predictive of toxicity and efficacy of irinotecan. This phase II study aimed to evaluate the combination of high-dose FOLFIRI plus bevacizumab in patients with previously untreated metastatic colorectal cancer (MCRC) based on their UGT1A1 genotype. Patients with the UGT1A1 *1/*1 (group 1) or *1/*28 (group 2) genotype received bevacizumab plus high-dose FOLFIRI every 2 weeks. Using the Bryant and Day design with objective response rate and toxicity as the primary endpoints, 54 patients in each group were required with a planned interim analysis after inclusion of 17 patients per group. We planned to stop the trial at the interim analysis if ≤7 patients exhibited an objective response (OR) and/or ≥3 patients exhibited severe toxicity. At the interim analysis, ORs were higher than the number expected: 52.9% (group 1) and 58.8% (group 2). More than three toxic events occurred in both groups and, according to the interim analysis rule, the trial was closed due to unacceptable toxicity. Recruitment was stopped when 86 patients were included and an analysis on overall population was done for overall survival (OS) and progression-free survival (PFS). The median PFS was 10.7 months (group 1) and 10.4 months (group 2). The median OS was 25.5 months (group 1) and 23.9 months (group 2). This trial does not support the use of the intensive treatment with HD-FOLFIRI plus bevacizumab combination for MCRC in patients with the UGTA1*1/UGT1A1*1 or UGT1A1*1/UGT1A1*28 genotype. Mol Cancer Ther; 14(12); 2782–8. ©2015 AACR. more...

3550 Background: In the early 2000s, classic LV5FU2 (C) (folinic acid, 5FU bolus, then 5FU infusion on D1 and D2) was replaced with simplified LV5FU2 (S) (folinic acid and 5FU bolus on D1 only), considered as effective and less toxic. No trial proved this assertion. The LV5FU2 companion in the FOLFIRI or FOLFOX regimen was C or S. The FFCD 2001-02 study compared in a 2 x 2 factorial design, in not-pretreated elderly patients (75+) with metastatic colorectal cancer, C or S, with or without irinotecan. No significant differences in PFS and OS were observed in the comparison with or without irinotecan. The median OS was 15.2 months in C versus 11.4 months in S, HR = 0.71 (0.55–0.92) and objective response rate was 37.1% in C vs S 25.6% in S, p = 0.004. The aim of this study was to present the factors associated with these differences. Methods: Prognostic factors associated with OS were studied using a Cox model. The multivariate analysis used the significantly different items from the univariate analysis and the differences observed at the inclusion. For each of these items, a subgroup analysis was performed. The second- and third-line treatments were analysed. Results: The 282 patients from the intent-to-treat study were included in the model. In OS, the prognostic factors were C versus S, number of metastatic sites, alkaline phosphatases (AP) and CEA. The interaction test in each subgroup for OS was not significant but C was significantly better in the following subgroup: age > 80 years, male, Karnofsky 100%, 1-2 Charlson index, AP ≤ 2N, leucocyte count > 11,000, CEA > 2N, CA 19-9 ≤2N. No differences were observed in the NCI toxicities but 130 serious adverse events in S versus 102 in C. A second-line was used for 55% patients in C, 46% in S, 81% of them with oxaliplatin or irinotecan in C, 76% after S. The third-line administration (20%) and targeted therapy (15%) were similar in C and S. Conclusions: C-LV5FU2 was superior both in subgroups with better and lower prognostics and this difference cannot be explained by an imbalance between the populations. The toxicity was not higher and a second-line was more often possible after C. The switch from C to S without scientific proof was perhaps a mistake in our practices. Clinical trial information: NCT00303771. more...

TPS3628 Background: Colon cancer (CC) occurs in around 50% of the patients after 70 years. Adjuvant chemotherapy (CT) has demonstrated a benefit on disease-free survival (DFS) and overall survival after a stage III CC resection. Nevertheless, adjuvant CT is poorly used in elderly patients. There is still concern about the efficacy of doublet CT with oxaliplatin in fit elderly patients and the usefulness of fluoropyrimidine monotherapy in unfit elderly patients. The selection of patients that should be treated remains a challenge. Geriatric evaluation and tumor biology should be explored to help for patient selection. Methods: ADAGE is a multicenter, randomized phase III study comparing 3-years DFS of 2 therapeutic strategies in 2 groups of patients aged over 70 with completely resected stage III CC. Patients are included in one of the 2 groups after a multidisciplinary team evaluation; Group 1 (arm A and B) is defined as “able” to be treated with doublet CT; Group 2 (arm C and D) is defined as “unable” to be treated with doublet CT. In each group, patients are randomized according to a 1:1 ratio. Randomization is stratified according to center, gender, stage (IIIA vs IIIB vs IIIC), occlusion and/or perforation (yes vs no) and independent activity of daily living score (IADL: normal vs abnormal). Arm A and D receive LV5FU2 or capecitabine, arm B FOLFOX4 or XELOX and arm C is an observation arm. The treatment is planned for 6 months. Adjuvant CT should start within 12 weeks after surgery. Geriatric questionnaires and Lee score must be completed before randomization. Radiological assessment is performed every 6 months for 3 years after randomization and then annually for 2 years. Hypotheses (α two-sided = 5%, power = 80%) are to improve 3-years DFS from 65% (arm A) to 72% (arm B) in group 1 (756 patients required) and from 40% (arm C) to 55% (arm D) in group 2 (226 patients required). Safety is evaluated based on laboratory and clinical tests before each cycle. Exploratory analysis are planned to determine geriatric prognostic factors for DFS. A biological ancillary study is planned to allow prognostic evaluation of mismatch repair status and other molecular signatures. At the 1stof February 2017 the accrual was 246 patients. Clinical trial information: NCT02355379. more...

Gastroenterology and Digestive Oncology, CHU Avicenne, APHP, Bobigny, France Oncology, Centre Antoine Lacassagne, Nice, France Oncogeriatry, ICM Val d’Aurelle, Montpellier, France Oncology, CH Senlis, Senlis, France Federation Francophone de Cancerologie Digestive, Burgundy University, INSERM U866, Dijon, France Geriatry, CHU Henri Mondor, APHP, Creteil, France Geriatry, Centre Gerontologique Departemental, Marseille, France Gastroenterology, CH de la Roche sur Yon, La Roche sur Yon, France Oncology, CHU Saint-Antoine, APHP, Paris, France rance Hepato-Gastroenterology and Digestive Oncology, CHU La Timone, APHM, Marseille, F more...

For resectable gastric cancer, both postoperative chemoradiotherapy and perioperative chemotherapy demonstrate high-level evidence for improved survival in Western populations. To evaluate the feasibility of pre- or postoperative chemoradiotherapy, we proposed two multicentre phase II studies.Patients with localised, histologically confirmed gastric cancer and Eastern Cooperative Oncology Group (ECOG) performance status2 judged suitable for curative resection were eligible. Eligible patients were assigned to either preoperative chemoradiotherapy followed by surgical resection or surgical resection followed by chemoradiotherapy depending on each centre. Chemoradiotherapy regimen included four courses of FOLFIRI (5 Fluorouracil, Leucovorin, Irinotecan) regimen then Concurrent fluorouracil at 200 mg/m2/d by continuous infusion 5 days each week. A dose of 50 Gy in 25 fractions in the preoperative study, or 45 Gy in 25 fractions in the postoperative study, was delivered. The primary end-point for both studies was the proportion of patients, who completed the therapeutic sequence.Between September 2007 and January 2010, 63 patients were included in both studies. The postoperative study was stopped for futility at the first step. In the preoperative study, 31 patients (73.8%, confidence interval (CI) 95%: 65.8-90.1%) received complete therapeutic sequence. Serum albumin and dietary restriction evaluated by QLQ-STO22 (Quality of Life-Stomach module) score were significantly linked with chemoradiotherapy feasibility in univariate analysis with respectively Odds-ratio (OR) 1.16 [CI 95%: 1.01-1.33] and 0.17 [0.03-0.89], p=0.04. Median overall survival time was 26.4 months in the preoperative study.Feasibility of chemoradiotherapy was not achieved for these studies: 73.8% (CI 95%: 65.8-90.1) and 42.9% (CI 95%: 21.8-66%) in preoperative and postoperative settings respectively. more...

3513Background: Optimal therapeutic strategy in patients (pts) with RCSM remains discussed and many front line options can be discussed to best treat primary tumor and metastatic disease: surgery (... more...

3532Background: Previous studies showed that high and low body mass index (BMI) are associated with worst prognosis in early-stage colorectal cancer (CRC) and low BMI is associated with a worst pro... more...

Background There is no consensus about the most effective method for transarterial chemoembolisation of hepatocellular carcinoma. Aim The aim of this phase II trial was to compare the efficacy and toxicity of lipiodol transarterial chemoembolisation with amiodarone in association with pirarubicin or doxorubicin versus lipiodol transarterial chemoembolisation with anthracycline alone in a control group. Methods Patients with unresectable hepatocellular carcinoma and Child-Pugh A/B7 were considered eligible for the trial. transarterial chemoembolisation was repeated every 6 weeks for a maximum of 4 sessions. Results Thirteen patients were randomised in the amiodarone group, and 14 were randomised in the control group. The two groups were comparable with respect to their baseline characteristics. The objective response rate according to the EASL criteria was 62% (95% CI 35–88) in the amiodarone group and 50% (95% CI 24–76) in the control group. At 1 and 2 years, survival rates were 77% (95% CI 44–92) and 52% (95% CI 22–75) in the amiodarone group, and 57% (95% CI 28–78) and 40% (95% CI 15–65) in the control group, respectively. There was no difference between the two groups in terms of toxicity. Conclusions The results of this study suggest that lipiodol transarterial chemoembolisation with anthracycline and amiodarone was safe but did not increase survival compared with lipiodol transarterial chemoembolisation with anthracycline alone in patients with hepatocellular carcinoma. more...

Background Several trials have studied the role of altered fractionation radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. Objectives The aim of this individual patient data (IPD) meta-analysis was to assess whether this type of radiotherapy could improve survival. Search methods We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; CENTRAL (2010, Issue 3); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 8 August 2010. Selection criteria We identified randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic head and neck squamous cell carcinomas and grouped trials into three pre-specified treatment categories: hyperfractionated, accelerated and accelerated with total dose reduction. Trials were eligible if they began recruitment after 1969 and ended before 1998. Data collection and analysis We obtained updated individual patient data. Overall survival was the main outcome measure. The secondary outcome measures were local or regional control rates (or both), distant control rates and cause-specific mortality. Main results We included 15 trials with 6515 patients. The median follow up was six years. Tumour sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (UICC 2002). There was a significant survival benefit with altered fractionation radiotherapy, corresponding to an absolute benefit of 3.4% at five years (hazard ratio (HR) 0.92, 95% CI 0.86 to 0.97; P = 0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at five years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at five years, P = 0.02). There was a benefit in locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at five years; P < 0.0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (under 50 year old) (HR 0.78, 95% CI 0.65 to 0.94), 0.95 (95% CI 0.83 to 1.09) for 51 to 60 year olds, 0.92 (95% CI 0.81 to 1.06) for 61 to 70 year olds, and 1.08 (95% CI 0.89 to 1.30) for those over 70 years old; test for trends P = 0.007). Authors' conclusions Altered fractionation radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation provides the greatest benefit. An update of this IPD meta-analysis (MARCH 2), which will increase the power of this analysis and allow for other comparisons, is currently in progress. more...

3541 Background: AVEX study has demonstrated increased progression-free survival (PFS) with capecitabine + bevacizumab compared to capecitabine alone in pts aged over 70 with mCRC. The treatment wi... more...

Introduction Resection remains the best treatment for local control of oesophageal carcinoma (OC), but local recurrence, distant metastasis and poor survival remain an issue after surgery. Often investigated in locally advanced OC, the impact of neoadjuvant chemoradiotherapy (NCRT) is unknown in patients with stage I or II OC. The aim of this multicentre randomised controlled phase III trial was to assess whether NCRT improves outcomes for patients with stage I or II OC. Methods 195 patients were randomly assigned to surgery alone (S group, n=98) or to NCRT group (NCRT group, n=97; 45Gy given in 25 fractions over 5 weeks with two courses of concomitant chemotherapy by 5-Fluorouracil 800 mg/m 2 on days 1–4 and cisplatin 75 mg/m 2 on day 1 or 2). The primary endpoint was overall survival. Secondary endpoints were progression free survival, postoperative morbidity and 30-day mortality, R0 resection rate and prognostic factor identification. Analysis was done by intention to treat. Results Patient and tumour characteristics were well-balanced between the two groups. Patients were preoperatively staged I in 18%, IIA in 49.7%, IIB in 31.8%, unknown in 0.5%. Postoperative morbidity and 30-day mortality rates were 49.5% vs 43.9% (p=0.17) and 1.1% vs 7.3% (p=0.054) in the S group and NCRT group, respectively. After a median follow-up of 5.7 years, 106 deaths were observed. Median survivals were 43.8 vs 31.8 months, respectively (HR 0.92, 95% CI 0.63 to 1.34, p=0.66). The trial was stopped due to futility. Conclusion Compared with surgery alone, NCRT with cisplatin and 5-Fluorouracil does not improve overall survival but enhances postoperative mortality for patients with stage I or II OC (Clinical Trial.gov identifier NCT 00047112). Funding Funded by the French ministry of Health—Programme Hospitalier de Recherche Clinique 1999. Competing interests None declared. more...

4108 Background: In locally advanced gastric cancer, perioperative chemotherapy (CT) is often recommended. The chemoradiotherapy (CTRT) interest is supported by the high risk of regional recurrence. The aim of this trial was to assess the feasibility of complete treatment (CT+CTRT+surgery) with a CT regimen efficient and well tolerated in metastatic phase. Methods: Histologically proven gastric carcinoma, with T3 and or N+, M0 according to CTscan or endoscopic ultrasound, WHO status ≤ 1 and allowing major surgery were eligible in this phase II multicenter study. The treatment consisted of 4 courses of FOLFIRI followed by concomitant CTRT (45 Gy at 1.8 Gy per fraction in 5 weeks, 5FU 200 mg/mg2 days 1 to 5 each week of radiotherapy), followed by surgical resection with partial or total gastrectomy according to the localization of the tumor 30 days after, with D1 or D2 lymphadenectomy. A complete treatment was defined by full CT courses, at least 22.5 fractions of RT (90% fractions) and 75% of the 5FU dose,... more...

4005 Background: Resection remains the best treatment for carcinoma of the esophagus regarding local control but local recurrence, distant metastatis and poor survival remain an issue after surgery... more...

The aim of the study was to investigate the residual blood level of O before each cycle of various oxaliplatin (O) based protocols, and to explore its predictive value for potential occurrence of a severe neurotoxicity. Methods: Between 11/2005 and 06/2008, 220 Pts were included in a prospective cohort, in 7 French centers. Patients received a minimum of 7 cycles of O. Blood samples were taken before each cycle with a maximum of 12 cycles. In parallel neurotoxicity was assessed by the modified Levi score (grade 0 to 3) and by the Von Frey filament exam. Saliva was collected before the first cycle for genomics analysis. The O concentration was obtained by Atomic Absorption Spectrometry assay after nitric digestion of total blood. Polymorphism of different targets were investigated (carrier proteins: MRP2, OCT1, OCT2, GSTP1, adducts repair system: ERCC1, ERCC2). Time to first severe neurotoxicity occurrence (TTSN Events: Grade 2 or3) was estimated using Kaplan-Meier. Predictive value of severe neurotoxicity was explored using univariate and multivariate logistic or Cox regressions. Harrel C index was produced. Results: 206 pts with gastro-intestinal cancer had, at the time of analysis, completed follow-up and 201 pts (91.3%) were eligible for pharmacokinetics. (85%) received FOLFOX regimen (85mg/m2every 2 weeks), the others GEMOX or XELOX (100mg/m2 every 3 weeks). The mean total dose of O received for all pts was 1.18 ± 0.4 g. After cycle 1, 2 and 10, median residual level of O was respectively 0.31 mg/L, 0.43 mg/L and 0.60 mg/L. The maximal concentration was obtained between cycle 5 and cycle 9. Respectively 89 Pts (44%) and 15 pts (7%) had a Gr2 and a Gr3 neurotoxicity. Median time TTSN was 141 days (95% CI: 132 – 161). O concentration before 2nd cure (HR = 1.39, p < 0.0001) is associated with TTSN (cure N°2 for Gr0 and Gr1, cure N° 7 for Gr2 and Gr3) but not with the frequency. Multivariate logistic and Cox analyses confirmed these results. Conclusions: 1. The mean residual blood level of O before the second cure is correlated with the occurrence of Gr2 or Gr3 neurotoxicity (p Mann-Whitney = 0.0007) 2. The residual blood level of O before the second O cure is correlated with the delay of occurrence of a Gr2 or Gr3 neurotoxicity in patients receiving an O based-regimen (Harrel C=0.54, p=0.021). Further statistical analyses will be done to analyse the data from the Von Frey filaments and the gene polymorphism and will be presented at the meeting. An O posology adaptation or infusion duration modification based on Platinum residual level of cure 1 have to be considered in future clinical trial in order to avoid severe Gr2 or Gr3 neurotoxicity. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C129. more...

e17544 Background: The FFCD phase III trial in pts with MPA comparing LV5FU2-P followed by gemcitabine (arm A) versus the opposite sequence (arm B) had failed to demonstrate a significant difference in median OS. To longitudinally compare QoL according to treatment sequence we have explore definitions of time until definitive deterioration (TUDD) of QoL scores according to minimal clinically important difference (MCID) cut off. Methods: From August 2003 to May 2006, 202 pts with measurable MPA, PS 0–2, non prior CT were included in 33 centers, 102 in arm A and 100 in arm B. QoL was evaluated using EORTC QLQ-C30 every 8 wks up to death. We focused analyses on the following scores: global health (GH), emotional functioning (EF), physical functioning (PF), fatigue (FA), and pain (PA). TUDD were estimated using Kaplan Meier, and compared using log-rank tests. They were defined as the time interval between randomization and the first occurrence of a decrease in QLQ-C30 score ≥ 5 points without any further improvement in QoL score ≥ 5 points or any further available QoL data. These analyses were repeated using a 10 points MCID, and by including deaths as event. Results: Amongst the 202 pts, 179 had completed at least one QoL questionnaire (89%) and the mean number of available QoL data was 3 (SD: 2.14). Using a 5 points MCID as well as 10 points, TUDD of the 5 scores did not differ according to treatment arm. About 25% of patients reported definitive score deteriorations≥ 5 points and 15%≥ 10 points. Including death as event for a 5 points MCID, median TUDD of GH score was 5.2 months (4.3–6.2) in Arm A and 6.1 months (5.1–6.1) in Arm B (log rank p = 0.50). Median TUDD of FA score was 4.8 months (3.5–6.3) in Arm A and 5.6 months (4.2–7.7) in Arm B (log rank p = 0.76). Median TUDD of scores was reached after median PFS and at median time of second-line PFS. While treatment had no impact, multivariate Cox model showed that tumor localization and progression were independently associated with TTDU (p < 0.05). Conclusions: We have investigated QoL analyses modalities using survival techniques dealing with binding drop out missing data and with an easier clinical interpretation of results. Progression seems to negatively impact QoL. No significant financial relationships to disclose. more...