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World Congress on Gastrointestinal Cancer, Barcelona, 2007.

Introduction

During the 9th World Congress on Gastrointestinal Cancer, more than 3000 attendees and experts discussed the progress on various aspects of the different gastrointestinal tumours. The meeting focused on the clinical aspects of the diagnosis and management of gastrointestinal tumours. Several sessions focused also on the underlying mechanisms causing cancers and on screening of gastrointestinal cancer. The modern multidisciplinary management of gastrointestinal cancer was stressed in many sessions. The meeting included many educational sessions, discussion forums, 'Meet the professor' sessions and abstract sessions in which data from new studies were presented. The outcome of a consensus discussion on rectal cancer was presented at the end of the meeting.

The most important progress in gastrointestinal cancer is in the areas of understanding the molecular mechanisms involved in carcinogenesis, the activity of the novel targeted agents, the prognostic and predictive role of molecular markers, and the optimal strategy and multidisciplinary management of gastrointestinal cancer.

Targeted agents

Hepatocellular carcinoma

The novel targeted agents have an increasing role in several gastrointestinal cancers. In the Sorafenib HCC Assessment Randomized Protocol (SHARP) trial led by J Llovet and J Bruix, patients with hepatocellular carcinoma were randomly assigned to sorafenib (400 mg twice daily, orally) or placebo. The median survival and time to tumour progression were significantly longer in patients treated with sorafenib, thus sorafenib has now become a new reference in hepatocellular carcinoma.

Pancreatic cancer

Despite major advances in the knowledge of the molecular mechanisms underlying pancreatic cancer, progress in the treatment has been relatively limited. The combination of gemcitabine plus erlotinib is slightly, but significantly, better than gemcitabine alone in advanced pancreatic cancer. Overall survival, however, remains low. New strategies in pancreatic cancer are therefore urgently needed to focus on new and more active agents and on better selection of the patients who might benefit from the various treatment options. J Spano presented the promising results of a randomised Phase II trial of gemcitabine plus axitinib versus gemcitabine alone in patients with advanced pancreatic cancer. Axitinib is an oral vascular endothelial growth factor receptor (VEGFR) 1, 2 and 3 inhibitor. Addition of axitinib reduced the hazard ratio (HR) for death by 26% compared with gemcitabine alone. In the subgroup of patients with good performance status, the HR for death was reduced by 33% (HR, 0.67) in favour of the combination with axitinib.

Colorectal cancer

In colon cancer, data showing the activity of the biological agents bevacizumab, cetuximab and panitumumab led the discussion on the optimal strategy for the management of metastatic disease. Important new data coming from the Bevacizumab Regimens Investigation of Treatment Effects and Safety (BRITE) study were presented; they suggested the improved outcome of patients when bevacizumab is continued beyond progression and when the cytotoxic backbone is changed (from irinotecan- to oxaliplatin-based or vice versa).

In the Cetuximab Combined With Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer (CRYSTAL) study, patients with metastatic colorectal cancer were randomly assigned to folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) or FOLFIRI plus cetuximab. The progression-free survival, the response rate and the number of patients that could undergo a resection of initially unresectable metastases were greater for patients treated with FOLFIRI/cetuximab.

The data of the Panitumumab Advanced Colorectal Cancer Evaluation (PACCE) study were presented for the first time. J Hecht from Los Angeles, USA showed in a large randomised Phase III study that patients treated with a cytotoxic combination [majority folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX), but also some FOLFIRI] plus bevacizumab and panitumumab suffered from an increased toxicity compared to those treated with the same combination without panitumumab. Moreover, the progression-free survival and overall survival was shorter for the four-drug combination compared to the three-drug combination. To date, there is no adequate explanation for these surprising findings. Other studies with panitumumab in combination with two cytotoxic agents and studies with four-drug combinations including bevacizumab and cetuximab are ongoing, as reviews of the Independent Data Monitoring Committee have so far revealed no relevant problems.

Interesting data on the response prediction for treatment with cetuximab and irinotecan in irinotecan-refractory patients showed the possible role of K-Ras mutation. Indeed patients with the wild-type K-Ras seem to have a better outcome when treated with cetuximab and irinotecan. It is, however, unlikely that determination of K-Ras status on its own will be the only predictive factor. A combination of different parameters is probably needed.

The new data in colorectal cancer led to discussion on important strategies to further improve the outcome of patients treated with the different available options (Panel 1). Questions such as what is the optimal combination regimen, the optimal treatment sequence and the optimal selection of patients need to be answered in future trials. Moreover, how more patients with initially unresectable disease can be rendered resectable needs to be investigated.

Gastrointestinal stromal tumour

In patients with neuroendocrine tumours, several new trials showing the activity of the mammalian target of rapamycin (mTOR)-inhibitor, everolimus, and of sunitinib were presented. The activity of sunitinib in imatinib-refractory gastrointestinal stromal tumour (GIST) has been shown, as has the fact that sunitinib is active against primary KIT exon 11 mutants and secondary mutants of the ATP binding site, which are resistant to imatinib.

Multidisciplinary and multimodal treatment

Colorectal cancer

Important data were also presented on the multidisciplinary and multimodal treatment of metastatic colorectal cancer and gastric cancer. B Nordlinger presented the European Organisation for Research and Treatment of Cancer (EORTC) 40983 study in patients with up to four resectable liver metastases of colorectal cancer. In this Phase III trial, patients were randomly assigned between surgery alone and peri-operative chemotherapy (i.e. 3 months of pre-operative FOLFOX and 3 months of post-operative FOLFOX) in combination with resection. Patients treated with peri-operative chemotherapy plus surgery had a clinically relevant improvement in progression-free survival. This conceptual trial led to the conclusion that in resectable metastatic colorectal cancer, peri-operative chemotherapy becomes a standard option. The EORTC is further building on this study with the new Biologicals Oxaliplatin Surgery (BOS) study in which patients with resectable liver metastases are randomly assigned to FOLFOX/cetuximab with or without bevacizumab.

Gastric cancer

In resectable gastric cancer, the concept of peri-operative chemotherapy was confirmed in a French study presented by P Rougier of Boulogne, France. Indeed this study showed an improved disease-free survival and overall survival for patients treated with a peri-operative chemotherapy in addition to surgical resection of the gastric cancer, compared to surgery alone. A Roth presented for the first time the results of the randomised Phase II trial of a Swiss group showing that pre-operative neoadjuvant chemotherapy was easier to administer than postoperative adjuvant chemotherapy. Abstracts of this meeting can be found in Annals of Oncology, 2007, 18, (suppl 7).

Eric Van Cutsem

Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium

Correspondence to: Eric Van Cutsem (email: eric.vancutsem@uz.kuleuven.ac.be)
PANEL 1: Strategies for improved outcome of
patients with metastatic colorectal
cancer

* Strategic patient management
 ** Administering most optimal treatment in first line
 ** Maximising options in subsequent lines
* Integration of targeted agents
* Resection of metastases whenever feasible
 ** Patient selection
 ** Patient characteristics--pharmacogenomics
 ** Tumour characteristics--molecular markers,
genetic signature
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Author:Van Cutsem, Eric
Publication:Advances in Gastrointestinal Cancer
Article Type:Conference notes
Geographic Code:4EUSP
Date:Jun 1, 2007
Words:1182
Previous Article:Annual meeting of the American Society of Clinical Oncology (ASCO), 2007.
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