Prognostic Relevance of Weight and Weight Loss during Multimodal Therapy for Oesophagogastric Tumours.

The prognostic meaning of weight loss (WL) during standard treatment for operable oesophagogastric cancer is still unclear. The aim of this study is to analyse the prognostic effect of WL during perioperative chemotherapy (PC) for gastric cancer (GC) and oesophageal adenocarcinomas (OAC). We retrospectively analysed data from 128 patients (pts) with GC and OAC who underwent surgery in the context of multimodal treatment with PC. We collected data on WL during different steps of therapy together with other histopathologic and demographic information. We analysed the effects on overall survival (OS) and disease-free survival (DFS). Results: Pts with WL ≥ 5% during neoadjuvant chemotherapy exhibited significantly worse OS compared with pts with WL < 5% (median OS: 23.6 months [95% CI: 4.4−42.9] vs. 63.5 months [95% CI: 50.7−76.2], p = 0.007) and DFS (median DFS: 12.5 months [95% CI: 2.9−22.1] vs. 63.5 months [95% CI: 31.6−95.4], p = 0.016). Pts with WL ≥ 14% during the whole treatment exhibited significantly worse OS compared with pts with WL < 14% (median OS: 43.7 months [95% CI: 13.2−74.2] vs. not reached, p = 0.028) and DFS (median DFS: 34.3 months [95% CI: 14.0−54.5] vs. not reached, p = 0.038). Conclusion: WL patterns during neoadjuvant chemotherapy and during the whole treatment correlate with a significantly worse prognosis in operated pts with curative GC or OAC in the context of a multimodal treatment with PC. A validation of this prognostic effect in prospective studies is warranted.

Impact of Postoperative Chemotherapy in Patients with Gastric/Gastroesophageal Adenocarcinoma Treated with Perioperative Chemotherapy.

Perioperative chemotherapy is the standard of care for patients undergoing curative resection for gastroesophageal adenocarcinoma. However, less than 50% of patients complete postoperative chemotherapy, and the added benefit to preoperative chemotherapy remains unclear. The aim of this study was to compare disease-free and overall survival (DFS and OS) in patients with perioperative chemotherapy to those who received preoperative chemotherapy only. In addition, a current literature overview is included. This multicenter, retrospective case series included 124 patients with gastroesophageal adenocarcinoma undergoing potentially curative resection and receiving pre- or perioperative chemotherapy between 2006 and 2010. Histopathological, demographic, clinical, and survival data were used to identify the impact of perioperative vs. preoperative chemotherapy on DFS and OS. Patients with perioperative chemotherapy had significantly improved DFS and OS (median DFS 28.0 months; 95%CI 0-62.4 vs. 19.0 months; 95%CI 10.5-27.5; p = 0.008 and median OS 35.7 months; 95%CI 0-73.6 vs. 19.2 months; 95%CI 7.8-30.4; p = 0.002). However, in contrast to patients with tumor-free lymph nodes at the time of resection, patients with positive lymph node status did not significantly benefit from additional postoperative chemotherapy in subgroup analysis. Further studies are encouraged to investigate optimal adjuvant treatment strategies for primary chemotherapy-resistant patients.

High Impact of Histopathological Remission for Prognosis after Perioperative Chemotherapy with ECF and ECF-Like Regimens for Gastric and Gastroesophageal Adenocarcinoma.

BACKGROUND: Perioperative chemotherapy with epirubicin, cisplatin and 5-fluorouracil (5-FU) (ECF)-like regimens is the European standard for patients with adenocarcinoma of the gastroesophageal junction (GEJ) or gastric body (GaCa) stage UICC II/III (staged according to the Union for International Cancer Control). However, limited data exist on the histopathological response and relevance of prognosis for patients homogeneously treated with ECF(-like) therapies. METHODS: All patients with GEJ/GaCa treated from September 2004 to September 2008 by perioperative ECF(-like) chemotherapy were retrospectively analyzed. Cisplatin and 5-FU were substituted with oxaliplatin or capecitabine when indicated. The histopathological response was assessed using the Becker score. RESULTS: Seventy-seven patients were analyzed with a median follow-up of 72.3 months. R0 resection was achieved in 53 of 68 operated patients. Recurrence was observed in 25 (32.5%) of these curatively treated patients, whereas 53/77 patients (68.8%) died, 39 (50.6%) of whom tumor related. The 5-year overall survival (OS) for the intention-to-treat population was 36.3%, and the 5-year tumor-specific survival was 42.2%. Pathological complete response (pCR) was seen in 10 patients (13.0%) and near pCR in 3 patients (3.9%). Patients with pCR had a significantly prolonged 5-year OS of 80.0 versus 29.7% compared to the nonhistopathological complete remission group (p = 0.01). CONCLUSION: In our retrospective analysis, ECF(-like) pretreatment resulted in a (near) pCR rate of 16.9%. In line with other regimens, our data suggest that histopathological response predicts the OS in patients treated with ECF(-like) regimens.

Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO).

BACKGROUND: The value of second-line therapy for metastatic gastric cancer is unclear. So far there are no randomised phase III data comparing second-line chemotherapy to best supportive care (BSC). In this prospective, multicenter, open label, randomised phase III study we compared irinotecan to BSC to evaluate the impact on survival of second-line chemotherapy. METHODS: Eligible patients (pts) had metastatic or locally advanced gastro-oesophageal junction or gastric adenocarcinoma, objective tumour progression during or within 6months after first-line chemotherapy and ECOG performance status 0-2. Stratification for time of progression after first-line therapy, ECOG PS and pretreatment secured even distribution of important prognostic factors. TREATMENT: Arm A: Irinotecan 250mg/m(2)q3w (first cycle) to be increased to 350mg/m(2), depending on toxicity. Arm B: BSC. FINDINGS: Between 10/2002 and 12/2006 40 pts were randomised. The study was closed prematurely due to poor accrual. Responsefor arm A (19 pts evaluable): No objective responses, SD 53%, PD 47%. Improvement of tumour related symptoms: Arm A 50% of pts, arm B 7%. Overall Survival: (all events in 40 pts have occurred): The hazard ratio for death was reduced to 0.48 (95%CI 0.25-0.92) in the irinotecan-arm (p=0.012). Median survival arm A: 4.0months (95% CI 3.6-7.5), arm B: 2.4months (95% CI 1.7-4.9). INTERPRETATION: Irinotecan as second-line chemotherapy significantly prolongs overall survival compared to BSC in the studied pts. Second-line chemotherapy can now be considered as a proven treatment option for metastatic or locally advanced gastric cancer. FUNDING: The study was supported by a research grant from Aventis and Pfizer.

Hepatic arterial infusion chemotherapy for liver metastases from gastric cancer: an analysis in Western patients.

AIMS AND BACKGROUND: The advantage of administering chemotherapy by hepatic arterial infusion is the achievement of high drug concentrations in the liver. Oxaliplatin, irinotecan and 5-flourouracil are active agents in advanced gastric cancer. Therefore a retrospective analysis was performed to investigate the effects of these drugs administered by hepatic arterial infusion in heavily pretreated gastric cancer patients with predominant hepatic metastases. Very limited data about hepatic arterial infusion exist in western gastric cancer patients. METHODS: Seven patients with advanced gastric cancer were included in the retrospective analysis. All patients had proven progressive disease prior to initiation of hepatic arterial infusion. All had an ECOG performance status of < or =2 and had received at least two previous systemic chemotherapy regimens, including the combination of cisplatin/5-fluorouracil. Patients were given chemotherapy by hepatic arterial infusion: 5-fluorouracil, 600 mg/m2, together with folinic acid, 300 mg/m2/2 h, followed by oxaliplatin, 85 mg/m2/2 h, every 2 weeks. RESULTS: Fifty-four cycles of hepatic arterial infusion (range, 2-21) with a median treatment duration of 6 cycles were administered in 7 patients. The treatment was feasible and safe, no grade 3-4 toxicity was observed. One patient showed stabilization of liver metastases over 7 months. In 6 of the 7 patients there was radiologically proven progressive disease after a median treatment time of 10 weeks. CONCLUSIONS: Chemotherapy by hepatic arterial infusion is modestly effective in heavily pretreated gastric cancer patients. Hepatic arterial infusion has a very favorable toxicity profile and can be safely administered even in elderly patients. It might be an additional therapeutic option and should be further investigated. The literature on hepatic arterial infusion in gastric cancer patients is reviewed.