Gastroesophageal adenocarcinomas – Neoadjuvant and adjuvant treatments in 2011: A review

Les adénocarcinomes oesogastriques (AOG) représentent une des premières causes de décès par cancer dans le monde. Alors que l’incidence de l’adénocarcinome (ADK) gastrique diminue, celle de l’ADK de la jonction oesogastrique augmente dans les pays occidentaux. Le traitement chirurgical étant le seul traitement curatif et le taux de survie à 5 ans dépendant du stade pTNM, la prise en charge thérapeutique est un véritable challenge pour les oncologues. Plusieurs modalités de traitement dont la chimiothérapie systémique ont été évaluées afin de diminuer les récidives et d’augmenter la survie globale. Cet article fait la mise au point en 2011 des traitements adjuvants et néoadjuvants des AOG. Aux États-Unis, la radiochimiothérapie postopératoire est préférée chez les patients en bon état général ayant un AOG réséqué (> stade Ia) mais n’est applicable que chez moins de la moitié des patients. Plus récemment, les FNCLCCFFCD et la UK MAGIC ont clairement démontré que la chimiothérapie périopératoire avait un bénéfice sur la survie globale des patients opérables pour leur AOG ; ce traitement est un standard et il est couramment réalisé en Europe. De nouvelles stratégies comme la chimiothérapie d’induction suivie d’une radiochimiothérapie, l’addition de thérapies ciblées à la chimiothérapie périopératoire ou l’utilisation de nouveaux schémas de chimiothérapie sont en cours d’évaluation afin d’augmenter le bénéfice des traitements standard actuels

Neoadjuvant Docetaxel-Based Chemoradiation for Resectable Adenocarcinoma of the Pancreas

International audienceTo assess the safety and efficacy of a new neoadjuvant chemoradiation (CRT) docetaxel-based regimen in patients with resectable adenocarcinoma of the pancreatic head or body

Reverse transcription-quantitative polymerase chain reaction: description of a RIN-based algorithm for accurate data normalization

<p>Abstract</p> <p>Background</p> <p>Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is the gold standard technique for mRNA quantification, but appropriate normalization is required to obtain reliable data. Normalization to accurately quantitated RNA has been proposed as the most reliable method for in vivo biopsies. However, this approach does not correct differences in RNA integrity.</p> <p>Results</p> <p>In this study, we evaluated the effect of RNA degradation on the quantification of the relative expression of nine genes (<it>18S</it>, <it>ACTB</it>, <it>ATUB</it>, <it>B2M</it>, <it>GAPDH</it>, <it>HPRT</it>, <it>POLR2L</it>, <it>PSMB6</it> and <it>RPLP0</it>) that cover a wide expression spectrum. Our results show that RNA degradation could introduce up to 100% error in gene expression measurements when RT-qPCR data were normalized to total RNA. To achieve greater resolution of small differences in transcript levels in degraded samples, we improved this normalization method by developing a corrective algorithm that compensates for the loss of RNA integrity. This approach allowed us to achieve higher accuracy, since the average error for quantitative measurements was reduced to 8%. Finally, we applied our normalization strategy to the quantification of <it>EGFR</it>, <it>HER2 </it>and <it>HER3 </it>in 104 rectal cancer biopsies. Taken together, our data show that normalization of gene expression measurements by taking into account also RNA degradation allows much more reliable sample comparison.</p> <p>Conclusion</p> <p>We developed a new normalization method of RT-qPCR data that compensates for loss of RNA integrity and therefore allows accurate gene expression quantification in human biopsies.</p

Christine Montoto-Grillot (9) and Michel Ducreux (10) . (1) Institut Paoli-calmettes

A phase II study of radiation and Docetaxel and Cisplatin in the treatment of locally advanced pancreatic carcinoma. FNCLCC-ACCORD 09/0201 trial. Radiotherapy has to be interrupted in 7 pts. 30 pts experienced at least one episode of grade 3 or 4 toxicity (asthenia 12 pts, anorexia 11 pts, vomiting 10 pts, nausea 9 pts, abdominal pain 5 pts). No toxic death was observed. 6 pts underwent secondary pancreatic resection (4 compete resection and 1 pt with histological complete remission). The objective response rate (CR 5 pts, PR 3 pts), was 16% with a median duration of 7.6 months. At 6 months, 30 pts had progressed. Median progression free survival was 5.8 months. With a 21 months median follow up, median overall survival was 9.6 months and 18 months survival rate of 31%. Conclusion: The association docetaxel+cisplatin+radiotherapy has limited effect in patients with locally advanced pancreatic carcinoma but major objective responses have been observed allowing secondary resections. Grant by Sanofi-Aventis, Amgen and Ligue Nationale Contre Le Cancer

Two consecutive phase II studies of oxaliplatin (L-OHP) for treatment of patients with advanced colorectal carcinoma who were resistant to previous treatment with fluoropyrimidines

Background Oxaliplatin (L-OHP) is a platinum complex that possesses activity against human and murine cells in vitro and in vivo, including colorectal carcinoma-derived cell lines, and cells that have been selected for resistance to cisplatin. We report two consecutive phase H trials of L-OHP for treatment of patients with advanced colorectal carcinoma. Patients and methods: Fifty-eight patients were entered in study I, and 51 patients in study II. All of the patients had tumor progression when they were treated, prior to their enrolment, with a fluoropyrimidine-containing regimen. In both trials treatment consisted of L-OHP, 130 mg/m2 by i.v. infusion for two hours; the treatment was repeated every 21 days. Results Response to therapy: Study I: Fifty-five patients were assessed for response. The response rate was 11% (95% CI, 0.03-0.19). Study II: All 51 patients were assessed for response. The response rate was 10% (95% CI, 0.017-0.18). The overall response rate for the 106 evaluated patients was 10% (95% CI, 0.046-0.16). Times to disease progression in responders were 4, 4, 4.5+, 5, 5, 6, 6, 6, 6+, 9, and 13 months. The dose-limiting toxic effect was sensory peripheral neuropathy. The incidence of severe peripheral neuropathy grades was: Study I: grade 3, 23% of patients, and grade 4, 8% of patients. Study II: grade 3, 14% of patients, and grade 4, 4% of patients. Severe neuropathy had a favorable course in all of the patients who had long-term neurologic follow-up. Diarrhea and myeloid impairment were minor. Conclusion L-OHP produced modest, but definite antitumor activity in patients with advanced colorectal carcinoma who were previously resistant to chemotherapy including fluoropyrirnidines. Toxicity is within acceptable limits of tolerance at the dose and schedule of oxaliplatin used in this tria

Subgroup analysis of patients with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) in the CORRECT trial who had progression-free survival (PFS) longer than 4 months

No abstract availabl