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AGICC: The Academic GI Cancer Consortium

 

GI Cancer Facts

GASTROINTESTINAL CANCERS:

Globally, and as a group, GI cancers cause more deaths than breast and lung cancers combined. The types of GI cancers include:

 

Colorectal Cancers (CRC)

With the newfound efficacy of the EGFR inhibitors, cetuximab and panitumimab, and the VEGF inhibitor, bevacizumab, in combination with 5-fluorouracil (or capecitabine), irinotecan and/or oxaliplatin, the outcome for patients with disseminated CRC has been greatly improved. Response rates to initial therapy exceed 60 percent and the median survival for disseminated CRC may exceed two years. Still, well over 90 percent of patients with stage IV CRC will die of their disease.

The dilemma for those involved in clinical and translational research against colorectal cancers is how and when to introduce new agents. This is further complicated because many clinicians are changing chemotherapy regimens but continuing to administer EGFR (cetuximab/panitumimab) and VEGFR (bevacizumab) inhibitors. Significantly, the proven activity of these targeted agents against colorectal cancer makes this class of tumor fertile ground for drugs that will work in concert with standard chemotherapy and the currently approved targeted agents.

 

Esophageal and Gastric Cancers

For many years, there have been a number of active agents and combinations of agents that may cause temporary remission of tumor and symptoms for patients with gastric and esophageal cancers. Nevertheless, large Phase III trials have not shown median survival beyond nine months for those with disseminated gastric or esophageal cancer. Moreover, in these tumors, the EGFR and VEGF inhibitors, alone or in combination, have not yet been adequately tested for their influence on outcome.

Phase II trials integrating novel agents into the first-line treatments for patients with advanced gastric and esophageal cancers should be a high priority because tumors of the gastroesophageal junction are increasing in frequency, and effective new targeted agents have not yet been found to influence the outcome for patients with gastric and esophageal cancer.

 

Pancreatic Cancer

Of the GI malignancies frequently treated in the West, the need for new and effective targeted agents is greatest for patients with pancreatic cancer. The choices of "standard" treatments for patients with disseminated adenocarcinoma of the pancreas are generally limited to gemcitabine and capecitabine, and the median survival for this group of patients is rarely reported at greater than four months.

However, because toxicity to agents such as gemcitabine, capecitabine and erlotinib are generally mild, many more patients with disseminated pancreas cancers are now good candidates to receive second-line treatments. Still, the "clinically insignificant" 12-day improvement in overall median survival gained by adding the EGFR inhibitor, erlotinib, to gemcitabine led to FDA approval for this combination for patients with locally advanced or metastatic pancreatic cancer-indicating the desperate situation facing patients with this disease.

 

Hepatocellular and Biliary Cancers

Globally, hepatocellular cancer is the third-leading cause of cancer deaths, and its incidence has dramatically increased in the West because it is closely associated with the epidemic of hepatitis C. In general, patients with hepatocellular cancer cannot undergo surgery or intensive chemotherapy because they have poor liver function. Adriamycin and fluoropyrimidines, two agents that have exhibited minimal activity against hepatocellular cancers, require relatively normal liver function in order to avoid severe toxicities. The hypothesis that hepatocellular cancers may respond to targeted agents has been recently confirmed.

Sorafenib, a multi-kinase inhibitor, tested against a placebo, improved median overall survival for patients with hepatocellular cancer from 7.9 months to 10.4 months. Some billary tumors can also be quite responsive to chemotherapy. Although this is a major step forward, knowledge of which tumors will respond to approved or available agents would be extremely useful for investigators and clinicians, as rapid deterioration of performance status often precludes second-line treatment-a fact that also underscores the need for additional new agents against this cancer.

 

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