Oxaliplatin, irinotecan and cetuximab in advanced gastric cancer: First results of a multicenter phase II trial (AGMT Gastric- 2

Woell, Ewald; Greil, R.; Eisterer, Wolfgang; Fridrik, Michael A.; Grünberger, Birgit; Gattringer, K.; Mayrbäurl, Beate; Russ, Gudrun; Thaler, J.

doi:10.1200/jco.2008.26.15_suppl.15587

Cited by 14 publications

(13 citation statements)

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“…In two phase II studies in advanced gastric cancer, combined irinotecan and oxaliplatin yielded a median TTP of 5.5 and 5.3 months, and an OS of 8.5 and 9.5 months (Souglakos et al, 2004;Woell et al, 2006). When irinotecan was used in combination with docetaxel in 90 untreated patients with advanced gastric cancer enrolled in two phase II studies, a median TTP of 3.8 and 4.5 months with an OS of 8.2 and 9.0 months were observed (Hawkins et al, 2003;Park et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Irinotecan, docetaxel and oxaliplatin combination in metastatic gastric or gastroesophageal junction adenocarcinoma

Lauro¹,

Nunziata

Arena

et al. 2007

Br J Cancer

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This phase II study was designed to evaluate the activity and safety of a combination of irinotecan, docetaxel and oxaliplatin in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Forty patients with measurable distant metastasis received irinotecan 150 mg m À2 and docetaxel 60 mg m À2 on day 1, and oxaliplatin 85 mg m À2 on day 2. Cycles were repeated every 3 weeks. The primary end point was to demonstrate a 50% improvement in time-to-progression (TTP) over historical controls. All patients were evaluable. Median TTP was 6.5 months (95% confidence interval (CI) 5.6 -7.4), the overall response rate was 50% (95% CI 35 -65%) and the median overall survival was 11.5 months (95% CI 8.7 -14.3). Grade 3/4 neutropaenia occurred in 47.5% of patients. There were four episodes of febrile neutropaenia in three patients. Other non-haematological grade 3 toxicities included diarrhoea in four patients (10%), vomiting in three patients (7.5%) and mucositis in two patients (5%). The irinotecan, docetaxel and oxaliplatin combination chemotherapy is an active and well-tolerated novel regimen for treating metastatic gastric or GEJ adenocarcinoma and deserves further evaluation in randomised trials and in combination with molecular targeting agents.

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Section: Discussionmentioning

confidence: 99%

Irinotecan, docetaxel and oxaliplatin combination in metastatic gastric or gastroesophageal junction adenocarcinoma

Lauro¹,

Nunziata

Arena

et al. 2007

Br J Cancer

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“…In the Austrian GASTRIC-II trial, the combination of oxaliplatin, irinotecan, and cetuximab has been applied in 51 patients with advanced GC [36]. In 35 patients accessible for response evaluation, there was an overall response rate (ORR) of 23% with a median time to progression (TTP) of 24.8 weeks and a median OS of 38.1 weeks for patients with wild-type status of the K-ras gene.…”

Section: Treatment Of Gastric Cancermentioning

confidence: 99%

Helicobacter pylori: Gastric Cancer and Extragastric Intestinal Malignancies

et al. 2012

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The greatest challenge in Helicobacter pylori-related diseases continues to remain prevention of gastric cancer. New evidence supports the beneficial effect of H. pylori eradication not only on prevention of gastric cancer but also on the regression of preneoplastic conditions of the gastric mucosa. Concerning early detection of gastric cancer there are still no adequate means and there is urgent need to define appropriate markers, for example, by gen-ome-wide research approaches. Currently, the best available method is the "serologic" biopsy based on pepsinogen I and the pepsinogen I/II ratio for identification of patients with severe gastric atrophy at increased risk for gastric cancer development. The treatment of early gastric cancer by endoscopic techniques can be performed safely and efficiently, but patients need meticulous follow-up for detection of metachronous lesions. In case of advanced disease, laparoscopically assisted surgical procedures are safe and favorable compared to open surgery. Two phase III trials support the role of adjuvant systemic treatment with different regimens. Unfortunately, there is still only slow progress in the development of palliative treatment regimens or modification of the existing therapy protocols. There is accumulating evidence for a role of H. pylori infection also in colorectal carcinogenesis. Seropositive individuals are at higher risk for the development of colorectal adenomas and consequently adenocarcinomas of this anatomical region. This phenomenon can partly be attributed to the increase of serum gastrin as response to atrophic changes of the gastric mucosa. In 2012, the infection with Helicobacter pylori remains one of the most challenging infectious diseases of the world, causing high morbidity and mortality. The major burden in global health care is still given by H. pylori representing the main risk factor for gastric cancer (GC), the second leading cause of cancer-related death. During the past years, the progress in the clinical management of GC has been modest. Innovations are limited to modifications of the existing chemotherapy regimens in either palliative or perioperative settings. Furthermore, new data have been gained concerning the endoscopic treatment of early GC. This review summarizes recent clinical-and research-related advances in the field of H. pylori and GC that have been published between April 2011 and April 2012, including also recent insights concerning the association between H. pylori infection and colorectal neoplasias. Prevention and Screening of Gastric Cancer H. pylori infection leads in all infected individuals to a chronic active gastritis, which can proceed, via the so-called Correa cascade, to gastric mucosal atrophy and intestinal metaplasia (IM), and finally to the development of GC. Thus, atrophy and IM are considered as precancerous conditions, and H. pylori eradication therapy is considered as preventive for GC [1]. Several studies have proven that eradication therapy also improves, or at least prevents, progression of ...

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“…Many first-line phase II trials have evaluated cetuximab in combination with various chemotherapy regimens [Pinto et al 2007[Pinto et al , 2009Woell et al 2008;Han et al 2009;Kanzler et al 2009;Kim et al 2009;Lordick et al 2010;Moehler et al 2010] showing an ORR in the range of 40-60%, time to progression 5.5-8 months, and OS 9.5-16 months. However, preliminary results of a randomized phase II study showed no clinically significant benefit when cetuximab was added to docetaxel plus oxaliplatin [Richards et al 2011] [Stein et al 2007;Tebbutt et al 2008;Li et al 2010].…”

Section: Targeting Her2mentioning

confidence: 99%

Molecular targeted therapies in advanced gastric cancer: does tumor histology matter?

Wong

Yau

2012

Therap Adv Gastroenterol

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It is increasingly recognized that gastric cancer is a heterogeneous disease which may be divided into subgroups based on histological, anatomical, epidemiological and molecular classifications. Distinct molecular drivers and tumor biology, and thus different treatment targets and predictive biomarkers, may be implicated in each subtype. However, there is little evidence in the literature regarding the correlation among these different classifications, and particularly the molecular aberrations present in each subtype. In this review, we approach advanced gastric cancer (AGC) by presenting aberrant molecular pathways and their potential therapeutic targets in gastric cancer according to histological and anatomical classification, dividing gastric cancer into proximal nondiffuse, distal nondiffuse and diffuse disease. Several pathways are involved predominantly, although not exclusively, in different subtypes. This may help to explain the disappointing results of many published AGC trials in which study populations were heterogeneous regardless of clinicopathological characteristics of the primary tumor. Histological and anatomical classification may provide insights into tumor biology and facilitate selection of an enriched patient population for targeted agents in future studies and in the clinic. However, some molecular pathways implicated in gastric cancer have not been studied in correlation with histological or anatomical subtypes. Further studies are necessary to confirm the suggestion that such classification may predict tumor biology and facilitate selection of an enriched patient population for targeted agents in future studies and in the clinic.

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Oxaliplatin, irinotecan and cetuximab in advanced gastric cancer: First results of a multicenter phase II trial (AGMT Gastric- 2

Cited by 14 publications

References 0 publications

Irinotecan, docetaxel and oxaliplatin combination in metastatic gastric or gastroesophageal junction adenocarcinoma

Irinotecan, docetaxel and oxaliplatin combination in metastatic gastric or gastroesophageal junction adenocarcinoma

Helicobacter pylori: Gastric Cancer and Extragastric Intestinal Malignancies

Molecular targeted therapies in advanced gastric cancer: does tumor histology matter?

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