Given this context, we randomized stage II and stage III patients into 2 arms. We compared 8 cycles of Xelox with observation. Most recently, the Korean phase III CLASSIC study reported a significant benefit in DFS from adjuvant combination chemotherapy. Following D2 resection, patients with stage II-IIIb gastric cancer were randomly assigned to eight cycles of adjuvant capecitabine and oxaliplatin (CAPOX) or to observation alone. This positive study shows that a 6-month course of CAPOX after D2 gastrectomy improves 3 year DFS compared with surgery only (74% vs. 59%; p < 0.0001). Chemotherapy reduced the relative risk of disease recurrence, new disease occurrence, or death compared with surgery alone. The OS data are not yet mature; however, the data suggest an improvement in OS with capecitabine and oxaliplatin compared with surgery only (83% vs. 78%; p = 0.0493).10 An analysis after a median follow-up of 5 years is planned to conclusively establish the OS benefit of capecitabine and oxaliplatin in this setting.
5-year overall survival: 15%-54%Parkin DM, et al. CA Cancer J Clin. 2005;55:74
• (1) patients with apparent locoregional carcinoma(stages I to III or M0)(a) those who are medically fit and whose canceris resectable,(b) those who are medically fit but whose cancer isunresectable, and(c) those who are inoperable (medically unfit).• (2) those with obvious metastatic carcinoma (stage IVor M1).ΑΔΡΗ ΣΑΞΙΝΟΜΗΗ
Καξθίλνο ηνπ ζηνκάρνππκπιεξσκαηηθή Αθηηλνζεξαπεία• British Stomach Cancer Group (1994):– N = 436, ηάδην II – III [N = 63 (14%) κε ππνιεηπόκελε λόζν]– Όινη νη αζζελείο ππεβιήζεζαλ ζε γαζηξεθηνκή .– 3 ζθέιε: γαζηξεθηνκή vs +ΑΚΘ vs +ΥΜΘ.– ΑΚΘ: 4500/25 ± 500cGy boost (Ζεύγνο πξνζζην-νπίζζησλ πεδίσλ)– ΧΜΘ: MAF x 8 .• Σνπηθή ππνηξνπή (12 κήλεο): 26% vs 9% vs 15%Σν εύξνο ηεο δηαθνξάο δελ επαλαιακβάλεηαη ζηνπο60 κήλεο• 5-εηή επηβίσζε: 20% v 12% v 19% (NS).Hallissey MT et al. The second British Stomach Cancer Group trial ofadjuvant radiotherapy Or chemotherapy in resectable gastric cancer: five-year follow-up. Lancet 1994;343:1309-12.
Surgically (D2)resected Stage II,IIIA, or IIIB GC,6 weeks prior torandomizationNo priorchemotherapy orradiotherapyn=1035Capecitabine: 1,000mg/m2 bid, d1–14, q3wOxaliplatin: 130mg/m2, d1, q3wRANDOMIZATION1:1†n=520n=515• Primary endpoint: 3-year DFS‡• Secondary endpoints: overall survival and safety profile†Stratified by stage and country with age, sex, and nodal status as covariates‡GASTRIC project: 3-year DFS and 5-year overall survival are strongly associated,Burzykowski et al. ASCO 2009ΚΟΡΕΑΣΙΚΗ ΜΕΛΕΣΗCLASSIC8 cycles of XELOX (6 months)Observation: No adjuvant therapy
Stomach Cancer AdjuvantMulti-institutional Trial(Samit) trial.2x2 factorial randomized phase III trial to investigateweekly paclitaxel (PTX) followed by oralfluoropyrimidines (FPs) versus FPs alone as adjuvantchemotherapy in patients (pts) with gastric cancer.
Ajani JA et Al – JCO - 2005R0 vs R+pCRWhy preoperative treatments ?treated 40 patients 5-FU, paclitaxel and cisplatin, radiotherapy Followed by surgery(pCR) of 20%, R0 resection rate of 78%, and median survival beyond 36 months
ΠΡΟΕΓΧΕΙΡΗΣΙΚΗ και ΠΕΡΙΕΓΧΕΙΡΗΣΙΚΗ ΧΗΜΕΙΟΘΕΡΑΠΕΙΑ
Neoadjuvant Treatmentsimprove SV in 4 Random TrialsFNCLCC/FFCD (1995-2003)EORTC 40954MRC MAGIC Trial (1994-2002)Dutch FAMTX
Peri-operative chemotherapy...Two positive randomized trialsFNLCC-FFCD 9703MAGIC TRIALR RSurgery SurgeryCF x 2-3SurgeryCF x 3-4224 pt503 ptECF x 3SurgeryECF x 3Boige, Asco 2007Cunningham, NEJM 2006• Adk of thestomach orlower third of theoesophagus• Stage II or grater• Suitable forcurative resection
...Two positive randomized trialsMAGIC TRIAL FNLCC-FFCD 9703Primary endpoint: Overall Survival5-y OS: 24% vs 38%5-y OS: 23% vs 36%Peri-operative chemotherapy
Magic TrialConclusionsPerioperative chemotherapy in resectablecarcinoma of the stomach and distal esophagusresults in:• Tumor downsizing and downstaging ?• Increased PFS• Increased OSPeri-operative Chemo is now standard of care in Europe
Multidisciplinary approach for thecure of localised gastric cancerConclusions• Adjuvant treatment is efficient but cumbersome and badlytolerated after gastrectomy• The role of XRT in (neo)adjuvant TTT of gastric cancer isstill unclear• Peri-operative or neoadjuvant chemotherapy are bettertolerated and leave less patients behind• We needed huge meta-analyses to be convinced ofadjuvant therapy while only few studies were sufficient forthe peri-operative strategy!