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Background The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. Patients and methods The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses. Results A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years. Conclusions In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years., Highlights • A reduction of the number of cancer patients attending cancer centers was observed in France from January to July 2020. • This reduction was observed only for newly diagnosed patients. • The reduction of new diagnosis was more pronounced in women, for breast cancer, and prostate cancer, and nonmetastatic cancer. • No compensation was observed for the last months of 2020. The magnitude of delays may be larger in centers within the same country. • An estimation of the excess cancer death resulting from these delays is presented.

Tailored neoadjuvant treatment of locally advanced rectal cancer (LARC) may improve outcomes. The aim of this study was to determine early MRI prognostic parameters with which to stratify neoadjuvant treatment in patients with LARC.All patients from a prospective, phase II, multicentre randomized study (GRECCAR4; NCT01333709) were included, and underwent rectal MRI before treatment, 4 weeks after induction chemotherapy and after completion of chemoradiotherapy (CRT). Tumour volumetry, MRI tumour regression grade (mrTRG), T and N categories, circumferential resection margin (CRM) status and extramural vascular invasion identified by MRI (mrEMVI) were evaluated.A total of 133 randomized patients were analysed. Median follow-up was 41·4 (95 per cent c.i. 36·6 to 45·2) months. Thirty-one patients (23·3 per cent) developed tumour recurrence. In univariable analysis, mrEMVI at baseline was the only prognostic factor associated with poorer outcome (P = 0·015). After induction chemotherapy, a larger tumour volume on MRI (P = 0·019), tumour volume regression of 60 per cent or less (P = 0·002), involvement of the CRM (P = 0·037), mrEMVI (P = 0·026) and a poor mrTRG (P = 0·023) were associated with poor outcome. After completion of CRT, the absence of complete response on MRI (P = 0·004), mrEMVI (P = 0·038) and a poor mrTRG (P = 0·005) were associated with shorter disease-free survival. A final multivariable model including all significant variables (baseline, after induction, after CRT) revealed that Eastern Cooperative Oncology Group performance status (P = 0·011), sphincter involvement (P = 0·009), mrEMVI at baseline (P = 0·002) and early tumour volume regression of 60 per cent or less after induction (P = 0·007) were associated with relapse.Baseline and early post-treatment MRI parameters are associated with prognosis in LARC. Future preoperative treatment should stratify treatment according to baseline mrEMVI status and early tumour volume regression.El tratamiento neoadyuvante personalizado del cáncer de recto localmente avanzado (locally advanced rectal cancer, LARC) puede mejorar los resultados. El objetivo de este estudio fue determinar factores pronósticos precoces mediante RMN para estratificar el tratamiento neoadyuvante en pacientes con LARC. MÉTODOS: Todos los pacientes de un eensayo prospectivo de fase II, multicéntrico y aleatorizado (GRECCAR4-NCT01333709) se incluyeron en este estudio y se les realizó una RMN antes del tratamiento, 4 semanas después de la quimioterapia de inducción y después de completar la quimiorradioterapia (chemoradiation, CRT). Se evaluó la volumetría tumoral, el grado de regresión tumoral mediante RMN (MRI Tumor Regression Grade, mrTRG), la estadificación T, la estadificación N, el estado del margen de resección circunferencial (circumferential resection margin, CRM) y la presencia de invasión extramural vascular en la RMN (extramural vascular invasion, mrEMVI).Se analizaron 133 pacientes aleatorizados. La mediana de seguimiento fue de 41,4 meses (i.c. del 95%: 36,6-45,2). En 31 pacientes (23%) se diagnosticó una recidiva. En el análisis univariado de la situación basal, mrEMVI fue el único factor pronóstico asociado con un peor resultado (P = 0,0152). Después de la quimioterapia de inducción, un volumen tumoral más alto en la RMN (P = 0,019), una regresión del volumen tumoral ≤ 60% (P = 0,002), la afectación del CRM (P = 0,037), mrEMVI (P = 0,026) y un grado escaso mrTRG (P = 0,023) se asociaron con un mal resultado. Después de completar la CRT, la ausencia de respuesta completa en la RMN (P = 0,004), la presencia de mrEMVI (P = 0,04) y una insuficiente mrTRG (P = 0,005) se asociaron con una supervivencia libre de enfermedad más corta. En el modelo multivariable final en el que se incluyeron todas las variables significativas (basales, postinducción, post-CRT), el estado de ECOG (P = 0,011), la afectación esfinteriana (P = 0,009), la presencia de EMVI al inicio (P = 0,002) y una regresión precoz del volumen tumoral ≤ 60% después de la inducción (P = 0,007) se asociaron con una recidiva. CONCLUSIÓN: Los parámetros basales y post-tratamiento precoces de la RMN se asocian con el pronóstico en el LARC. La estrategia terapéutica preoperatoria futura deberá estratificar el tratamiento de acuerdo con la presencia de EMVI al inicio y la regresión precoz del volumen tumoral.

Background Currently, metastatic colorectal cancer is treated as a homogeneous disease and only RAS mutational status has been approved as a negative predictive factor in patients treated with cetuximab. The aim of this study was to evaluate if recently identified molecular subtypes of colon cancer are associated with response of metastatic patients to first-line therapy. Patients and methods We collected and analysed 143 samples of human colorectal tumours with complete clinical annotations, including the response to treatment. Gene expression profiling was used to classify patients in three to six classes using four different molecular classifications. Correlations between molecular subtypes, response to treatment, progression-free and overall survival were analysed. Results We first demonstrated that the four previously described molecular classifications of colorectal cancer defined in non-metastatic patients also correctly classify stage IV patients. One of the classifications is strongly associated with response to FOLFIRI (P = 0.003), but not to FOLFOX (P = 0.911) and FOLFIRI + Bevacizumab (P = 0.190). In particular, we identify a molecular subtype representing 28% of the patients that shows an exceptionally high response rate to FOLFIRI (87.5%). These patients have a two-fold longer overall survival (40.1 months) when treated with FOLFIRI, as first-line regimen, instead of FOLFOX (18.6 months). Conclusions Our results demonstrate the interest of molecular classifications to develop tailored therapies for patients with metastatic colorectal cancer and a strong impact of the first-line regimen on the overall survival of some patients. This however remains to be confirmed in a large prospective clinical trial.

The sequential FOLFOX7–FOLFIRI combination is not superior to FOLFOX4 in colorectal cancer patients with resectable metastases. Patients with synchronous metastases preferably received perioperative chemotherapy, while patients with metachronous metastases were given postoperative chemotherapy in preference. We observed the highest long-term survival rates ever reported in this setting. Background Perioperative FOLFOX4 (oxaliplatin plus 5-fluorouracil/leucovorin) chemotherapy is the current standard in patients with resectable metastases from colorectal cancer (CRC). We aimed to determine whether a sequential chemotherapy with dose-dense oxaliplatin (FOLFOX7) and irinotecan (FOLFIRI; irinotecan plus 5-fluorouracil/leucovorin) is superior to FOLFOX4. The chemotherapy timing was not imposed, and was perioperative or postoperative. Patients and methods In this open-label, phase III trial, patients with resectable or resected metastases were randomly assigned either to 12 cycles of FOLFOX4 (oxaliplatin 85 mg/m2) or 6 cycles of FOLFOX7 (oxaliplatin 130 mg/m2) followed by 6 cycles of FOLFIRI (irinotecan 180 mg/m2). Randomization was done centrally, with stratification by chemotherapy timing, type of local treatment (surgery versus radiofrequency ablation with/without surgery), and Fong's prognostic score. The primary end point was 2-year disease-free survival (DFS). Results A total of 284 patients were randomized, 142 in each treatment group. Chemotherapy was perioperative in 168 (59.2%) patients and postoperative in 116 (40.8%) patients. Perioperative chemotherapy was preferentially proposed for synchronous metastases, whereas postoperative chemotherapy was more frequently used for metachronous metastases. Two-year DFS was 48.5% in the FOLFOX4 group and 50.0% in the FOLFOX7–FOLFIRI group. In the multivariable analysis, more than one metastasis [hazard ratio (HR) = 2.15] and synchronous metastases (HR = 1.63) were independent prognostic factors for shorter DFS. Five-year overall survival (OS) rate was 69.5% with FOLFOX4 versus 66.6% with FOLFOX7–FOLFIRI. Conclusions FOLFOX7–FOLFIRI is not superior to FOLFOX4 in patients with resectable metastatic CRC. Five-year OS rates observed in both groups are the highest ever reported in this setting, possibly reflecting the pragmatic approach to chemotherapy timing. Clinical trials number NCT00268398.

Background While tumor-tissue remains the ‘gold standard’ for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care. Patients and methods Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients). Results are presented according to STARD criteria and were discussed in regard with clinical outcomes of patients. Results Much more mutations were found by ctDNA analysis: 59%, 11.8% and 14.4% of the patients were found KRAS, NRAS and BRAF mutant by ctDNA analysis instead of 44%, 8.8% and 7.2% by tumor-tissue analysis. Median tumor-tissue data turnaround-time was 16 days while 2 days for ctDNA analysis. Discordant samples analysis revealed that use of biopsy, long delay between tumor-tissue and blood collection and resection of the tumor at time of blood draw, tumor site, or type of tissue analyzed seem to affect concordance. Altogether, the clinical data with respect to the anti-epidermal growth factor receptor response (RAS status) and the prognosis (BRAF status) of those discordant patients do not appear contradictory to the mutational status as determined by plasma analysis. Lastly, we present the first distribution profile of the RAS and BRAF hotspot mutations as determined by ctDNA analysis (n = 119), revealing a high proportion of patients with multiple mutations (45% of the population and up to 5 mutations) and only 24% of WT scored patients for both genes. Mutation profile as determined from ctDNA analysis with using various detection thresholds highlights the importance of the test sensitivity. Conclusion Our study showed that ctDNA could replace tumor-tissue analysis, and also clinical utility of ctDNA analysis by considerably reducing data turnaround time.

Supplementary methods: Flow cytometry experiments. Immunofluorescence studies. Surface plasmon resonance measurements. Cell migration assays. Apoptosis assay. (DOCX 37Â kb)

Distribution of patients with mCRC according to the tumor molecular subtype. (DOCX 33Â kb)

CLDN1 gene (222549_at.) expression. a, in 17 normal colorectal mucosa (NM), 20 primary tumor (PT) samples and 19 hepatic metastases (HM); *** = p

Most patients with pancreatic cancer present with advanced/metastatic disease and have a dismal prognosis. Despite the proven albeit modest benefits of gemcitabine demonstrated over a decade ago, subsequent advances have been slow, suggesting it may be time to take a different approach. It is thought that some key characteristics of pancreatic cancer, such as the desmoplasia, restricted vasculature and hypoxic environment, may prevent the delivery of chemotherapy to the tumour thereby explaining the limited benefits observed to-date. Moreover, there is evidence to suggest that the stroma is not only a mechanical barrier but also constitutes a dynamic compartment of pancreatic tumours that is critically involved in tumour formation, progression and metastasis. Thus, targeting the stroma and the tumour represents a promising therapeutic strategy. Currently, several stroma-targeting agents are entering clinical development. Among these, nab-paclitaxel appears promising since it combines cytotoxic therapy with targeted delivery via its proposed ability to bind SPARC on tumour and stromal cells. Preclinical data indicate that co-treatment with nab-paclitaxel and gemcitabine results in stromal depletion, increased tumour vascularization and intratumoural gemcitabine concentration, and increased tumour regression compared with either agent alone. Phase I/II study data also suggest that a high level of antitumor activity can be achieved with this combination in pancreatic cancer. This was recently confirmed in a Phase III study which showed that nab-paclitaxel plus gemcitabine significantly improved overall survival (HR 0.72) and progression-free survival (HR 0.69) versus gemcitabine alone for the first-line treatment of patients with metastatic pancreatic cancer. (C) 2013 Elsevier Ltd. All rights reserved

Summary Objectives The most commonly used schedules are 5-FU in combination with CDDP with or without epirubicin (ECF) or docetaxel (TCF) in treatment of MGA patients (pts), independently of HER status. We evaluated the efficacy of FOLFIRI regimen in a large retrospective series of MGA pts. Methods Two hundred and twelve pts from 13 French centers were treated with at least one cycle of FOLFIRI (irinotecan 180 mg/m 2 intravenous (i.v.) over 90 minutes on day 1 with folinic acid (FA) 400 mg/m 2 i.v. over two hours followed by 5-FU 400 mg/m 2 i.v. bolus then 5-FU 2400 mg/m 2 continuous infusion over 46 hours on day 1, repeated every 14 days). Primary tumour sites were 120 (58%) stomach and 92 (42%) gastroesophageal junction. FOLFIRI was administered as first-line in 137 (65%) pts and as later-line in 75 (35%) pts for MGA. Results There was no difference between chemonaive and not chemonaive pts treated as first-line in terms of response rate 37% (95% CI: 25–50) vs 44% (95% CI: 21–69), median PFS, 6.7 (95% CI: 5.5–9.9) vs 5.3 months (95% CI: 3.6–6.9) ( P = 0.25), and OS, 13.1 (95% CI: 11.7–18.7) vs 8.8 months (95% CI: 7.3–15.6) ( P = 0.19), respectively. There was no difference between pts treated as second or later-line in terms of response rate 20% (95% CI: 8–39) vs 22% (95% CI: 6–48), median PFS, four months (95% CI: 2.8–5.4) vs 3.5 months (95% CI: 2.3–4.5) ( P = 0.56), and OS, 10.4 months (95% CI: 5.4–14.4) vs 5.3 months (95% CI: 3.5–11.3) ( P = 0.58), respectively. The global grade 3–4 toxicities were: diarrhea 11%, vomiting 9%, neutropenia 18%, febril neutropenia 4% (one toxic death). Conclusions This retrospective study confirms the activity and good tolerance of FOLFIRI regimen in MGA as first-line as well as later-line.

This study compared superparamagnetic iron-oxide-enhanced magnetic resonance imaging (SPIO-MRI) and combined fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in evaluating liver metastases from colorectal adenocarcinoma following chemotherapy.Nineteen patients were included in this retrospective study. SPIO-MRI and PET/CT results were compared with surgery, intraoperative ultrasound and pathology results in 11 patients and with the follow-up in eight patients.SPIO-MRI and PET/CT identified 125 and 71 metastases, respectively. False negative lesions were 11 for SPIO-MRI and 65 for PET/CT. In the whole study population, the per-lesion analysis of SPIO-MRI and PET/CT showed a sensitivity of 92% and 52% (p0.001) and the per-segment analysis a sensitivity of 99% and 79% (p0.001), respectively. In patients who underwent surgery, the per-lesion analysis of SPIO-MRI and PET/CT showed a sensitivity of 85% and 58% (p0.05) and the per-segment analysis a sensitivity of 97% and 63% (p0.05), respectively. In patients who underwent follow-up, the per-lesion analysis of SPIO-MRI and PET/CT showed a sensitivity of 97% and 47% (p0.001) and the per-segment analysis a sensitivity of 100% and 63% (p0.007), respectively. For lesions ≥15 and30 mm and for lesions15 mm, SPIO-MRI demonstrated a higher sensitivity than PET/CT (p0.001).SPIO-MRI appears superior to PET/CT in evaluating liver metastases from colorectal adenocarcinoma following chemotherapy.

We compared clinical outcome and pharmacokinetic (pK) parameters of a new pharmacokinetically-guided dosing strategy in two groups of patients (ageor65 years) with metastatic colorectal cancer (mCRC). We retrospectively analyzed all the patients with mCRC, receiving standard LV5FU2 regimen during cycle-1, intensified from cycle-2 onwards according to an adaptation schedule based on the area under the concentration-time curve (AUC) value (mg.h/l.m(2)) of 5-FU measured during cycle-1. Among the 103 eligible patients, the 48 elderly (median age 70 range 65-80) did not differ significantly from the 55 non-elderly patients (median age 59 range 33-64) in pPK parameters (including AUC at cycle-1 and cycle-2), efficacy (objective response rate of 27% [16.1-40.9] in younger and 35% [22.2-50.5] in older patients, p = 0.4) and tolerability (33.3% of overall grade 3-4 toxicities in older patients and 34.5% in younger, p = 0.9). Our data indicated high dose-intensity values, not significantly different between elderly and non-elderly patients. it was feasible to increase the 5-fU continuous infusion dose in 43/55 (78%) younger and 40/48 (83%) older patients (p=0.509) and even to double it in half of the patients of both groups. Aging did not seem to limit intensified chemotherapy or to affect the pK behavior of the 5-FU.

Summary Three 1.2% glutaraldehyde solutions of different commercial origin and which had been stored differently were used in 201 healthy and sick cattle for the glutaraldehyde test on whole blood. The three solutions reacted differently. Two of them gave too quick gelling times which made them unsuitable for the clinical use of the test, viz. detection of hypergammaglobulinaemia. These abnormally quick gelling times could be due to aldolic condensation of glutaraldehyde. The resulting polymers might be present in the commercially available reagents or/and may form during storage, especially at room temperature. This condition is a serious disadvantage for the use of the glutaraldehyde test in the field. Zusammenfassung Unterschiedliche Gerinnungszeiten bei Verwendung von drei Glutaraldehydlosungen fur den Glutaraldehydtest mit Rinderblut Mit drei 1,2%igen Glutaraldehydlosungen unterschiedlicher kommerzieller Herkunft, die verschieden gelagert worden waren, wurde der Glutaraldehydtest mit Vollblut von 201 gesunden und kranken Rindern durchgefuhrt. Die drei Losungen reagierten unterschiedlich. Zwei Losungen erwiesen sich als unbrauchbar zum klinischen Nachweis einer Hypergammaglobulinamie, da die Gerinnungszeiten viel zu kurz waren. Die abnorm schnelle Gerinnung wurde moglicherweise durch eine aldolische Kondensation des Glutaraldehyds verursacht. Die dadurch entstehenden Polymere konnen in kommerziellen Reagentien vorhanden sein oder im Verlauf der Lagerung, speziell bei Zimmertemperatur, entstehen. Dieser Umstand bedeutet einen ernsthaften Nachteil hinsichtlich der Anwendung des Glutaraldehyds in der Praxis. Resume Temps de coagulation differents en utilisant trois solutions de glutaraldehyde pour le test a la glutaraldehyde avec du sang de bovin Le test a la glutaraldehyde a ete effectue avec du sang complet de 201 bovins sains et malades en utilisant trois solutions de glutaraldehyde a 1,2% d'origine commerciale differente et conservees differemment. Les trois solutions ont reagi de maniere differente. Deux solutions se sont revelees etre inutilisables pour la mise en evidence clinique d'une hypergammaglobulinemie etant donne que les temps de coagulation etaient beaucoup trop courts. La coagulation anormalement rapide a pu etre causee par une condensation aldolique de la glutaraldehyde. Les polymeres ainsi produits pouvaient etre presents dans les reactifs du commerce ou s'etre developpes durant l'entreposage, en particulier a la temperature ambiante. Cette situation signifie un desavantage serieux pour l'utilisation de la glutaraldehyde dans la pratique. Resumen Tiempos diferentes de coagulacion utilizando tres soluciones distintas de glutaraldehido para la prueba de glutaraldehido con sangre entera de vacunos Con tres soluciones de glutaraldehido al 1,2%, de diversos origenes comerciales, almacenadas diferentemente, se llevo a cabo la prueba de glutaraldehido con sangre entera de 201 reses vacunas sanas y enfermas. Las tres soluciones reaccionaron de modo desigual. Dos de las soluciones se mostraron como inservibles para la puesta en evidencia clinica de una hipergammaglobulinemia, ya que los tiempos de coagulacion eran demasiado breves. Esta coagulacion anormalmente rapida tal vez fuera ocasionada por una condensacion aldolica del glutaraldehido. Los polimeros asi resultantes pueden estar presentes en los reactivos comerciales o/y formarse en el curso del almacenamiento, en especial a temperaturas de habitacion. Esta circunstancia resulta ser una desventaja seria para aplicar el glutaraldehido en la practica.

Colorectal cancer remains a leading cause of cancer deaths. Over the last decade, many new drugs have emerged in the treatment of metastatic colorectal cancers. Thus, significant progress has been achieved with daily use of oxaliplatin, irinotecan, or similar oral 5-fluorouracil (capecitabine or UFT). The identification of new molecular targets has allowed the development of new antitumor agents directed against receptors for growth factor or cons key factors involved in the process of angiogenesis. Large randomized trials of metastatic colorectal cancer have demonstrated significant clinical benefit with bevacizumab (inhibiting the vascular endothelial growth factor VEGF) and inhibitors of epidermal growth factor receptor (EGFR), namely cetuximab and the panitumumab. In this article, we review the role and impact of mutational status of KRAS in the care of patients with colorectal cancer metastasis.

Background: A phase-III trial showed the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) in terms of efficacy in first-line treatment of metastatic colorectal cancer. A secondary objective was to compare the quality of life (QoL) and health-care satisfaction of patients. Methods: Patients were randomised to receive XELOX (n=156) or FOLFOX-6 (n=150) for 6 months. Quality of life and satisfaction were assessed by the Quality of Life Questionnaire-C30 (QLQ-C30) and Functional Assessment of Chronic Illness Therapy Chemotherapy Convenience and Satisfaction Questionnaire (FACIT-CCSQ), respectively. Patients completed questionnaires at baseline, at Cycle3 (C3) and Cycle (C6) (XELOX) or at C4 and C8 visits (FOLFOX-6) and at their final visit. Results: A total of 245 and 225 patients were assessed using QLQ-C30 and FACIT-CCSQ, respectively. The completion rates were >80%. Global QoL scores did not differ significantly between groups during the study. According to FACIT-CCSQ, XELOX seemed more convenient (C3/C4, P

This dose escalation study was designed to determine the maximum tolerated dose (MTD) and recommended doses (RDs) of 5-fluorouracil (5FU), folinic acid and oxaliplatin (FOLFOX) with concomitant radiotherapy in inoperable/metastatic oesophageal squamous cell carcinoma or adenocarcinoma. Patients received three courses of LV5FU2 regimen (folinic acid 200 mg m(-2), bolus 5FU 300-400 mg/m(2), continuous infusion 5FU 400-600 mg m(-2) on days 1 and 2) and escalating doses of oxaliplatin 50 to 100 mg m(-2) on day 1 (FOLFOX). This regimen was repeated every 2 weeks, concomitant to a 50-gray radiotherapy per 5 weeks. Three more cycles were delivered after completion of radiation therapy. Three to six patients were allocated to each of the five dose levels until MTD was reached. Thirty-three patients were enroled and 21 had metastatic disease. Maximum tolerated dose was oxaliplatin 100 mg m(-2), and continuous infusion 5FU was 600 mg m(-2) day(-) (level 5). The most common toxicities were neutropenia, dysphagia and oesophagitis. The RDs were those of FOLFOX-4 regimen (oxaliplatin 85 mg m(-2) and full doses of LV5FU2). The overall response was 48.5%, including 12% complete response. Response rate on primary tumour was 62.9%. This FOLFOX-4 regimen was reasonably well tolerated and effective in inoperable/metastatic oesophageal carcinoma and warrants additional investigation.

Malgrede recents progres dans la prise en charge des adenocarcinomes œsogastriques (AOG), leur mortalitereste elevee et leur traitement est encore un veritable challenge pour les oncologues. Le traitement chirurgical etant le seul traitement curatif et le taux de survie a cinq ans dependant du stade pTNM, plusieurs modalites de traitement, dont la chimiotherapie systemique, ont ete evaluees afin de diminuer les recidives et augmenter la survie globale. Cet article fait la mise au point des traitements adjuvants et neoadjuvants des AOG. Aux Etats-Unis, la radiochimiotherapie postoperatoire est preferee chez les patients en bon etat general ayant un AOG reseque (> stade la). Plus recemment, les FNCLCC-FFCD et la UK-MAGIC ont montre que la chimiotherapie peri-operatoire avait un benefice sur la survie globale des patients operables pour leur AOG et ce traitement est couramment realise en Europe. De nouvelles strategies comme la chimiotherapie d’induction suivie d’une radiochimiotherapie, l’addition de therapies ciblees a la chimiotherapie perioperatoire ou l’utilisation de nouveaux schemas de chimiotherapies sont en cours d’evaluation afin d’augmenter le benefice des traitements standard actuels.

To assess the rate of R(0) resection of liver metastases achieved after chemotherapy with FOLFIRINOX.Patients with histologically proven primary colorectal cancer and bidimensionally measurable liver metastasis, not fully resectable based on technical inability to achieve R(0) resection, but potentially resectable after tumor reduction, were given FOLFIRINOX: oxaliplatin 85 mg/m(2), irinotecan 180 mg/m(2), leucovorin 400 mg/m(2), bolus fluorouracil 400 mg/m(2) and fluorouracil 46-h continuous IV infusion 2,400 mg/m(2), every 2 weeks for a maximum of 12 cycles.Thirty-four patients were enrolled. Response rate before surgery was 70.6% (95%CI: 52.5-84.9). Twenty-eight patients (82.4%) underwent hepatic resection and nine achieved R(0) resection [26.5% (95% CI: 12.9-44.4%)]. The rate of clinical complete remission after surgery was 79.4%. Two-year overall survival was 83%. The most frequent grade 3 or 4 toxicities were neutropenia (64.8%), diarrhea (29.4%), fatigue (23.5%), abdominal cramps (14.7%), neuropathy and nausea (11.8% each), and AST/ALT elevation (14.7/11.8%). Only one patient experienced febrile neutropenia, four patients withdrew due to toxicity and no toxic death was observed.FOLFIRINOX, with an acceptable toxicity profile, shows a high response rate in liver metastases from colorectal cancer. The rate of hepatic resection in patients initially not resectable, is attractive and warrants further assessment of this regimen in randomized studies compared to standard regimens.

Background/Aims: To compare the cost consequences of oral capecitabine and two different intravenous regimens of 5-fluorouracil/folinic acid (de Gramont and Mayo Clinic regimens) as adjuvant therapy in stage III colon cancer in France. Methods: Clinical efficacy and safety data were taken from published clinical trials. Medical resource use was estimated from published data and expert opinion. Direct costs (drug acquisition, inpatient and home drug administration, laboratory tests, transportation, and management of adverse events) were considered over a time horizon of 46 months (3.8 years). The perspective taken was that of the French Sickness Funds. Results: In patients treated with capecitabine, relapse-free survival was 1.3 months longer than with the Mayo Clinic regimen, which has been shown to be as effective as the de Gramont regimen. In the base case analysis, capecitabine was less costly (3,654 EUR/patient) than the Mayo Clinic (10,481 EUR/ patient) and de Gramont (7,204 EUR/patient) regimens. In the sensitivity analysis, capecitabine remained dominant except when the intravenous regimens were assumed to be administered at home in all patients. Conclusions: In France, capecitabine is more effective and less costly than both the Mayo Clinic and de Gramont regimens as adjuvant therapy for colon cancer.

International audience

Introduction Depuis les vingt dernieres annees, des progres substantiels ont ete realises dans la prise en charge du cancer colorectal metastatique (CCRm). Recemment, des groupes independants ont propose de nouvelles classifications moleculaires (Sadanandam A, et al. Nat Med , 2013 ; De Sousa E, Melo, et al. Nat Med , 2013 ; Marisa L, et al. PLoS Med , 2013) du cancer colorectal fondees sur des profils d’expression genique de tumeurs primaires. Ces classifications realisees sur des echantillons de patients atteints pour la plupart de CCR de stades II–III ont conduit a l’identification de trois a six sous-types moleculaires. L’aspect pronostique des differentes classes moleculaires a ete etudie mais leur implication dans l’aide a la decision therapeutique n’a pas ete vraiment demontree meme si un lien entre les sous-types et les reponses aux drogues a ete suggere. Dans ce contexte, notre etude vise a evaluer si ces sous-types moleculaires sont indifferemment sensibles aux therapies utilisees dans le CCRm et leur correlation avec la survie globale (OS) et la survie sans progression (PFS). Methodes Nous avons utilise des echantillons de tumeurs primaires de 143 patients chimio-naifs issus de trois cohortes : REGP (etude prospective monocentrique), COSIVAL (etude retrospective multicentrique) et BIOCOLON (etude prospective multicentrique). Les patients ont ete traites selon differents schemas therapeutiques de premiere ligne : 79 patients ont recu une combinaison irinotecan/LV5FU2 (FOLFIRI), 22 patients du FOLFIRI associe a du bevacizumab, 32 patients une combinaison oxaliplatin/leucovorin/5-fluorouracil (FOLFOX) et 10 patients divers autres schemas (FOLFIRI/cetuximab : n = 1 ; FOLFIRINOX : n = 3 ; FOLFIRINOX/bevacizumab : n = 1 ; FOLFOX/bevacizumab : n = 4 ; XELIRI/bevacizumab : n = 1). La reponse tumorale a ete evaluee selon les criteres RECIST. Les 143 prelevements de tumeurs primaires colorectales ont ete hybrides sur la plateforme Affymetrix avec les puces Human Genome U133 Plus 2.0. Les donnees d’hybridation ont ete normalisees independamment pour chaque cohorte en utilisant la methode robust multi-array average (RMA) implemente dans le package R affy . Les donnees ont ensuite ete agregees selon la methode COMBAT pour enlever les effets batch (package R inSilicoMerging ). L’identification des sous-groupes moleculaires a ensuite ete realisee selon les procedures decrites dans les publications de reference. Resultats Nous avons ainsi demontre que : – les sous-types moleculaires identifies dans les trois publications originales sont tous presents dans nos donnees et peuvent etre utilises pour stratifier les patients atteints de CCRm ; – la classification de Marisa et al. ( PLoS Med , 2013) est correlee a la reponse au FOLFIRI ; – un sous-type moleculaire particulier est associe a une OS et PFS plus longue chez des patients traites avec du FOLFIRI. Conclusion En conclusion, nous avons demontre que le CCRm peut etre classifie en utilisant les memes sous-types moleculaires decrits precedemment dans les stades moins avances, et que la classification decrite par Marisa et al. est un predictive de la reponse au FOLFIRI mais pas a des schemas de type FOLFOX ou FOLFIRI/bevacizumab. Ces resultats montrent que le traitement des patients pourrait etre ameliore en analysant le profil moleculaire de leurs tumeurs, et egalement ouvrir la voie a des therapies individualisees avec une meilleure efficacite dans le cancer colorectal metastatique.

This multicenter, phase II, open-label study evaluated the antitumor efficacy and safety of oxaliplatin and raltitrexed (Tomudex) in non-pretreated advanced colorectal cancer patients.Seventy-one patients received oxaliplatin 130 mg/m(2) and raltitrexed 3 mg/m(2) intravenously on an outpatient basis every 3 weeks. All patients had histologically proven metastatic colorectal adenocarcinoma, performance statusor=2 and good baseline organ function. Most (56%) had only one disease site. All patients were assessed for safety, and 66 of 69 eligible patients were assessed for response.A total of 404 cycles were administered, with a median of six cycles per patient (range 1-12 cycles). Relative dose intensities were 0.98 and 0.98 for oxaliplatin and raltitrexed, respectively. The most common grade 3-4 toxicities (National Cancer Institute Common Toxicity Criteria) among treated patients were as follows: neutropenia (21 patients, 30%), asthenia (eight, 11%), diarrhea (12, 17%), liver function test abnormalities (24, 34%), nausea (nine, 13%) and vomiting (nine, 13%). Two treatment-related deaths occurred (hematotoxicity in one patient and gastrointestinal toxicity in the other) and two further deaths were possibly related to treatment (hepatic dysfunction in one patient and neuropathy in the other). Thirty-seven objective responses (one complete) were obtained [objective response rate 54%; 95% confidence interval (CI) 42% to 65%] in eligible patients. The median response duration was 8.5 months (95% CI 6.7-12.2 months), while median progression-free and overall survival among eligible patients were 6.2 (95% CI 5.1-6.9 months) and 14.6 months (95% CI 11.0-18.9 months), respectively.The present study confirms the feasibility of the raltitrexed plus oxaliplatin combination and its activity in non-pretreated advanced colorectal cancer patients.

Carcinoembryonic antigen (CEA) and CA 19-9 are both widely used in the follow up of patients with gastrointestinal cancer. More recently another tumor marker, named CA 72-4 has been identified and characterized using two different monoclonal antibodies B72.3 and CC49. Several reports evaluated CA 72-4 as a serum tumor marker for gastric cancer and compared its clinical utility with that of CEA or CA 19-9; few reports concerned its prognostic value. In the present study, CA 72-4 is evaluated and compared with CEA and CA 19-9 in various populations of patients with gastric cancer and benign disease; for 52 patients with gastric adenocarcinoma and 57 patients without neoplastic disease CEA, CA 19-9 and CA 72-4 were evaluated before treatment. Sensitivity of the tumor markers CA 72-4, CA 19-9 and CEA at the recommended cut-off level in all 52 patients were 58%, 50% the sensitivity increased to 75%. of these markers, for non metastatic patients, multivariate analyses indicated that none of the markers were significant, when adjusted for gender and age (which were indicators of poor prognosis); patients with abnormal values of CA72-4 tended to have shorter survival than patients with normal values (p< 0.07). In the metastatic population, only high values of CA19-9 (p< 0.02) and gender (women) (p< 0.03) were indicators of poor prognosis in univariate analysis; multivariate analysis revealed that both CA72-4 (p= 0.034) and CA19-9p= 0.009), adjusted for gender were independent prognostic factors. However, CA72-4 lost significance (p= 0.41) when adjusted for CA19-9 and gender, indicating that CA19-9 provides more prognostic information than CA72-4.When limited to the metastatic male population with normal values of CA 19-9 and CEA, CA 72-4 pretherapeutic positive levels were associated with a worse prognosis (p< 0.005).In conclusion, this study suggests that the addition of CA 72-4 to CEA and/or CA 19-9 could improve sensitivity in gastric cancer. The prognostic role of this marker is not yet clearly demonstrated but its usefulness in the monitoring of gastric cancer should be taken into account.

Unknown primary tumors are highly malignant diseases which portend a dire prognosis. We designed a prospective high dose-intensity policy with the aim of improving the results obtained with conventional chemotherapy.Chemotherapy regimens were determined according to clinical features. In patients younger than 61 years with an ECOG performance status of 0 or 1, poorly differentiated adenocarcinoma or poorly differentiated carcinoma, and no evidence of brain or bone marrow involvement (group A), the treatment plan included four sequential high-dose courses with hematopoietic progenitor cell and growth factor support. Peripheral blood progenitor cells were collected by apheresis as the leukocyte counts recovered from the nadir induced by the first cycle of chemotherapy (doxorubicin 75 mg/m2, cyclophosphamide 6000 mg/m2). Patients then received two cycles of etoposide (800 mg/m2) and carboplatin (900 mg/m2) separated by one cycle of doxorubicin (75 mg/m2) and cyclophosphamide (3000 mg/m2). G-CSF (5 micrograms/kg/d) was given until engraftment. It was planned that cycles would be delivered every three weeks. The remaining patients (group B) received alternative cycles of AC (doxorubicin 50 mg/m2, cyclophosphamide 1000 mg/m2) and EP (etoposide 300 mg/m2, cisplatin 100 mg/m2). Cycles were given at two-week intervals with GM-CSF support (5 micrograms/kg/d) from day 4 to day 10. Patients without measurable lesions were included, since the major endpoint was survival.Sixty patients entered the study. Twenty patients were assigned to group A and 40 patients to group B. In group A, 5 of 12 patients with measurable lesions (42%; 95% confidence interval (95% CI): 22%-62%) achieved major responses to chemotherapy, including one complete response. The duration of the overall median survival was 11 months. In group B, a major response was observed in 12 (39%; 95% CI: 28%-50%) of 31 patients with measurable lesions, including three complete responses. The overall median survival was 8 months. Hematological toxicities were noteworthy in both groups. Two toxic deaths occurred in group B.Using these doses and schedules of chemotherapy, a high-dose intensity policy does not appear to improve the outcome of patients with carcinoma of unknown primary site. Alternative studies dealing with new drugs are required.

Resume Propos. — Les carcinomes de site primitif inconnu constituent une entite clinique dont la frequence est elevee et dont la prise en charge quotidienne, tant diagnostique que therapeutique, demeure difficile. Methodes. — Cent patients pris en charge au centre regional de lutte contre le cancer de Montpellier pour un carcinome de site primitif inconnu ont fait l'objet d'une etude retrospective portant sur les caracteristiques cliniques et biologiques au moment du diagnostic, les examens realises lors du bilan initial, les traitements entrepris et l'evolution. Resultats. — Trois principaux types histologiques ont ete observes: adenocarcinome (66 patients), carcinome indifferencie (19 patients), et carcinome epidermoide (11 patients). Les sites metastatiques les plus frequemment envahis etaient les os, les poumons, les ganglions et le foie. Parmi les explorations complementaires realisees lors du bilan initial afin d'identifier la tumeur primitive (dont aucune, par definition, ne s'est averee contributive), 68 combinaisons differentes d'examens ont ete observees. Une anemie inferieure a 100 g/L a ete notee chez dix patients, alors qu'une elevation des phosphatase alcalines a ete observee chez 42 patients. Sept patients, decedes pendant ou au decours immediat du bilan initial, n'ont recu aucun traitement. Une chimiotherapie et une radiotherapie ont ete delivrees chez respectivement 70 et 59 patients, ces deux traitements ayant ete associes dans 36 cas. Un sel de platine a ete delivre chez 53 des 70 patients ayant recu une chimiotherapie. Le nombre median de cycles administre par patient a ete de quatre. Neuf reponses partielles ont ete observees, dont six chez des patients ayant recu une chimiotherapie comportant un sel de platine. Quatre-vingt-seize patients sont decedes, dont 95 a la suite de la progression de la maladie et un d'affection intercurrente. La survie mediane a ete de 9 mois. Deux variables pronostiques ont ete identifiees lors de l'analyse unifactorielle : le nombre de sites metastatiques et le taux serique des phosphatases alcalines. Conclusions. — Cette etude retrospective confirme les difficultes de prise en charge diagnostique et therapeutique des carcinomes de site primitif inconnu. L'analyse de la litterature permet de recommander, pour la pratique quotidienne, un bilan diagnostique limite ayant pour objectif principal d'identifier les tumeurs primitives susceptibles d'avoir un impact pronostique (sein et ovaire) ou therapeutique (prostate). En dehors des cas anatomocliniques particuliers, les indications et modalites de la chimiotherapie ne sont pas definies.

1Bayer HealthCare Pharmaceuticals, Montville, NJ, USA; 2University Hospital Gasthuisberg/Leuven, Leuven, Belgium; 3San Martino Hospital, Genoa, Italy; 4Ospedale Niguarda Ca’ Granda, Milan, Italy; 5University Hospital, Pisa, Italy; 6CRLC Val d’Aurelle, Montpellier, France; 7St-Luc University Hospital, Brussels, Belgium; 8Robert Debre University Hospital, Reims, France; 9Institut Sainte-Catherine, Avignon, France; 10Catholic University of Sacred Heart, Rome, Italy; 11Centre Oscar Lambret, Lille, France; 12Vall d’Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain; 13National Cancer Center Hospital East, Kashiwa, Japan; 14University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA; 15Ohio State University School of Medicine, James Cancer Hospital and Solove Research Institute, Columbus, OH, USA; 16Mayo Clinic, Rochester, MN, USA; 17Bayer Pharma AG, Berlin, Germany

International audience; BACKGROUND:The combination of bevacizumab and bolus 5-fluorouracil, leucovorin and irinotecan is highly effective in patients with metastatic colorectal cancer (mCRC). This randomised, multicenter, non-comparative phase II trial assessed the efficacy and safety of bevacizumab plus oral capecitabine plus irinotecan (XELIRI) or infusional 5-fluorouracil, leucovorin plus irinotecan (FOLFIRI) as first-line therapy for patients with mCRC.PATIENTS AND METHODS:Patients received bevacizumab 7.5mg/kg on day 1 plus XELIRI (irinotecan 200mg/m(2) on day 1 and oral capecitabine 1,000 mg/m(2) bid on days 1-14) every 3 weeks or bevacizumab 5mg/kg on day 1 plus FOLFIRI (5-fluorouracil 400mg/m(2) on day 1 plus 2,400 mg/m(2) as a 46-h infusion, leucovorin 400mg/m(2) on day 1, and irinotecan 180 mg/m(2) on day 1) every 2 weeks. Patients aged ≥ 65 years received a lower dose of capecitabine (800 mg/m(2) twice daily). The primary endpoint was 6-month progression-free survival (PFS) rate.RESULTS:A total of 145 patients were enrolled (bevacizumab-XELIRI, n=72; bevacizumab-FOLFIRI, n=73). The 6-month PFS rate was 82% (95% confidence intervals (CI) 71-90%) in the bevacizumab-XELIRI arm and 85% (95% CI 75-92%) in the bevacizumab-FOLFIRI arm. In both the bevacizumab-XELIRI and bevacizumab-FOLFIRI arms, median PFS and overall survival (OS) were 9 and 23 months, respectively. The most frequent toxicities were grade 3/4 neutropenia (bevacizumab-XELIRI 18%; bevacizumab-FOLFIRI 26%) and grade 3 diarrhoea (12% and 5%, respectively).CONCLUSIONS:This randomised non-comparative study demonstrates that bevacizumab-XELIRI and bevacizumab-FOLFIRI are effective regimens for the first-line treatment of patients with mCRC with manageable toxicity profiles.

ML18147 evaluated continued bevacizumab with second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) progressing after the standard first-line bevacizumab-containing therapy.Evaluating outcomes according to tumor Kirsten rat sarcoma virus oncogene (KRAS) status was an exploratory analysis. KRAS data were collected from local laboratories (using their established methods) and/or from a central laboratory (mutation-specific Scorpion amplification-refractory mutation system). No adjustment was made for multiplicity; analyses were not powered to detect statistically significant differences.Of 820 patients, 616 (75%) had unambiguous KRAS data; 316 (51%) had KRAS wild-type tumors and 300 (49%) had mutant KRAS tumors. The median progression-free survival (PFS) was 6.4 months for bevacizumab plus chemotherapy and 4.5 months for chemotherapy [P0.0001; HR = 0.61; 95% confidence interval (CI): 0.49-0.77] for wild-type KRAS and 5.5 and 4.1 months, respectively (P = 0.0027; HR = 0.70; 95% CI: 0.56-0.89) for mutant KRAS. The median overall survival (OS) was 15.4 and 11.1 months, respectively (P = 0.0052; HR = 0.69; 95% CI: 0.53-0.90) for wild-type KRAS and 10.4 versus 10.0 months, respectively (P = 0.4969; HR = 0.92; 95% CI: 0.71-1.18) for mutant KRAS. In both analyses, no treatment interaction by KRAS status was observed (PFS, P = 0.4436; OS, P = 0.1266).Bevacizumab beyond first progression represents an option for patients with mCRC treated with bevacizumab plus standard first-line chemotherapy, independent of KRAS status.

e15688Background: FOLFIRINOX (FFX) and nab-paclitaxel/gemcitabine (AG) showed significant improvement in efficacy compared to gemcitabine alone in metastatic pancreatic cancer (mPC). Alternating AG...

Epidermal growth factor receptor (EGFR) inhibitors are part of the therapeutic arsenal available for advanced cancer. However, they are frequently associated with cutaneous side-effects, which can hamper compliance, lead to treatment refusal and impair quality of life.To know the attitudes of French oncologists who deal with this skin toxicity. This work is one of the steps to build a therapeutic algorithm of side-effects induced by EGFR inhibitors taking both evidence-based medicine and standard practices into account.Physicians completed a questionnaire as part of regional meetings, before any discussion. Questions concerned the management of 11 clinical situations in the context of EGFR inhibitor prescription.Sixty-seven questionnaires were analysed. The collaboration with dermatologists was especially planned for persisting or worsening lesions beyond 2 weeks, but never considered at the time of the introduction of targeted therapy. The results demonstrated the difficulties encountered in diagnosing and grading skin lesions. Attitudes of oncologists were uniform for preventive care and management of mild lesions for which moisturizing and cyclines were widely prescribed. Significant differences appeared in the treatment of less typical cases such as the involvement of skin appendages, secondary infections of folliculitis or cases associated with radiodermatitis. Discrepancies existed also for what to do in relation with maintenance or interruption of EGFR inhibitor mainly if they were responsible for severe lesions.This original survey emphasizes the interest of greater multidisciplinary collaboration and the necessity to harmonize practice.

Combined chemotherapy has demonstrated a degree of efficacy in gastric carcinoma. As 5-fluorouracil (5FU) and cisplatinum are two of the most active drugs, we have tested the efficacy of combined 5FU and cisplatinum in a prospective phase II trial. Cycles were administered every 4 weeks and consisted of 5FU 1000 mg/m 2 /day 5 days continuous intravenous (i.v.) infusion and cisplatinum 100 mg/m 2 on day 2. Cycles were repeated according to tolerance and efficacy. 87 patients entered the study, 57 with metastatic or recurrent tumour (M) and 30 with locally advanced gastric cancer (LAGC). The response rate for the 83 evaluable patients was 43% [95% confidence interval (CI) 30–56%]. There were four complete responses (5%), 32 partial responses (39%), 34 cases of stable disease and 13 cases of progressive disease. Responses were more frequent in patients with a good performance status ( P = 0.02), with their primary located in the cardia ( P = 0.003), with a non-linitis plastica tumour form ( P = 0.003) or a tumour containing less than 50% of independent cells ( P = 0.016). Median survival was 9 months for the total population. It was better in patients with a good performance status ( P = 0.01), and those who did not have linitis plastica ( P = 0.005). Toxicity was acceptable, although grade 3–4 neutropenia was reported in 22% of the cycles, mucositis in 14% and 3 patients died of septic complications. The combination of 5FU and cisplatinum is effective in terms of tumour response in advanced gastric cancer and warrants testing with the other active regimens.

20 patients with liver metastases from colorectal carcinoma undergoing laparotomy received 15–60 mg intravenously, either intact or fragments of, anti-carcinoembryonic antigen (anti-CEA) monoclonal antobodies labelled with 0.55–1.48 GBq (15–40 mCi) of 131 I, 3–8 days prior to operation. The uptake measured per gram of metastases ranged from 0.33 to 6.6 × 10 −3 % of injected dose. Tumour to liver uptake ratios ranged from 2 to 33. The radiation dose, estimated in 6 patients (3 of each group), for an extrapolated dose of 3.7 GBq (100 mCi) of 131 I ranged from 0.3 to 0.8 Gy in normal liver or spleen (an acceptable estimate for bone marrow radiation dose) and from 3.4 to 8.2 Gy to the hepatic metastases, indicating that probably other therapeutic modalities should be associated with radioimmunotherapy.

Colorectal cancer remains a leading cause of cancer deaths. Over the last decade, many new drugs have emerged in the treatment of metastatic colorectal cancers. Thus, significant progress has been achieved with daily use of oxaliplatin, irinotecan, or similar oral 5-fluorouracil (capecitabine or UFT). The identification of new molecular targets has allowed the development of new antitumor agents directed against receptors for growth factor or cons key factors involved in the process of angiogenesis. Large randomized trials of metastatic colorectal cancer have demonstrated significant clinical benefit with bevacizumab (inhibiting the vascular endothelial growth factor VEGF) and inhibitors of epidermal growth factor receptor (EGFR), namely cetuximab and the panitumumab. In this article, we review the role and impact of mutational status of KRAS in the care of patients with colorectal cancer metastasis.

Objective: In a recent randomized study, we demonstrated that XELOX (oxaliplatin + oral capecitabine) was well tolerated and not inferior in terms of efficacy to the infusional FOLFOX-6 regimen in first-line treatment of metastatic colorectal cancer (mCRC). The objective of this additional analysis was to compare the cost of XELOX and FOLFOX-6. Methods: This cost-minimisation study took into account costs related to drug acquisition, hospital care for chemotherapy administration and for serious adverse event management. Hospital care costs were based on French ‘diagnosis-related group’ tariffs. Drug acquisition costs were drawn from French official sources. Analysis was performed from the French health insurance perspective. Results: Baseline characteristics of the 282 patients included (143 XELOX, 139 FOLFOX-6) were well balanced. Patients reported less and shorter hospitalisations (day and overnight hospital care) with XELOX: 6.4 ± 2.2 hospitalisations versus 9.7 ± 3.1 (p < 0.001); 11.4 ± 10.6 days versus 17.7 ± 11.8 (p < 0.001). Mean disease management cost per patient was significantly lower with XELOX (EUR 12,918 ± 5,075 vs. EUR 17,229 ± 8,665, p < 0.001). Conclusion: In the perspective of our analysis, taking into account hospitalisation and drug acquisition costs, the treatment of mCRC patients with XELOX in comparison to FOLFOX-6 significantly decreased the costs, as well as the mean overall hospitalisation length of stay.

Background: This multicenter adjuvant phase III trial evaluated the addition of irinotecan to LV5FU2 in colon cancer patients at high risk of relapse. Patients and methods: A total of 400 patients with histologically proven primary colon cancer with postoperative N1 detected by occlusion/perforation or N2 were randomised to: A-LV5FU2 [leucovorin 200 mg/m 2 , 2-h infusion, 5-fluorouracil (5-FU) 400 mg/m 2 bolus, 600 mg/m 2 22-h continuous infusion, days 1 and 2] or B-LV5FU2 + IRI (irinotecan 180 mg/m 2 90-min infusion day 1 + LV5FU2) fortnightly for 12 cycles. Primary end point was disease-free survival (DFS). Results: Median follow-up was 63 months. Significantly more T4 tumours and 15 or more positive lymph nodes were observed in arm B. 5-FU relative dose intensity (RDI) was >0.80 for 94% and 77% in arms A and B, respectively (P 0.80 for 70% patients. There were more grades 3 and 4 neutropenia in arm B (4% versus 28%, P < 0.001). The 3-year DFS was 60% [95% confidence interval (Cl) 53% to 66%] and 51 % (95% Cl 44% to 58) in arms A and B, respectively. No difference was observed [hazard ratio (HR) = 1.12, 95% Cl 0.85-1.47, P = 0.42] even when adjusted for prognostic factors (adjusted HR = 0.98, 95% Cl 0.74-1.31, P = 0.92). The 5-year overall survival (OS) was 67% (95% Cl 59% to 73%) and 61% (95% Cl 53% to 67%) in arms A and B, respectively. Conclusion: Adjuvant LV5FU2 + IRI compared with LV5FU2 alone in patients at high risk of relapse showed no improvement in DFS and OS.

Background To assess activity and safety of an experimental combination of irinotecan and oxaliplatin (IRINOX) as first-line treatment in advanced colorectal cancer. Patients and methods In this randomized phase II trial, 80 patients were treated: arm A (IRINOX) in 40 patients received at day 1 oxaliplatin 85 mg/m2 and irinotecan 180 mg/m2 biweekly, standard arm B received a biweekly simplified folinic acid (FA) and fluorouracil (FU), FA 200 mg/m2 in a 2-h infusion and bolus injection of 5FU 400 mg/m2 on day 1, then a two 400 mg/m2 continuous infusion of FU on days 1 and 2 with either oxaliplatin 85 mg/m2 (20 patients) or irinotecan 180 mg/m2 (20 patients). Results Twenty-one partial responses (52.5%, median duration 7.2 months) were observed with the IRINOX arm and two complete and 20 partial responses (55%, median duration 6.4 months) with arm B. Median progression-free and overall survival times were 8.4 and 19 months, respectively, in the IRINOX arm and 8.1 and 20.4 months in arm B. Main grade 3/4 toxic effects were, respectively, neutropenia 42.5% and 32.5%; febrile neutropenia 10% and 5%; diarrhea 32.5% and 7.5%; vomiting 10.0% and 5%; neurosensory toxicity 17.5% and 7.5%. Conclusion The IRINOX arm has a manageable toxicity and is active.