Randomized phase III trial comparing FOLFIRINOX (F 5FU/leucovorin [LV], irinotecan [I], and oxaliplatin [O]) versus gemcitabine (G) as first-line treatment for metastatic pancreatic adenocarcinoma (MPA) Preplanned interim analysis results of the PRODIGE 4/ACCORD 11 trial

SUMMARY: Adenocarcinoma of the pancreas is one of the hard-to-treat cancers for which chemotherapy has not demonstrated any survival benefit – that is, until now. In a recently presented randomized phase III trial at the ASCO 2010 meeting, 250 patients with metastatic pancreatic cancer were assigned to receive either single agent Gemcitabine (GEMZAR®) or a combination of fluorouracil, leucovorin, Irinotecan (CAMPTOSAR®) , and Oxaliplatin (ELOXATIN®) – (FOLFIRINOX regimen). Following an interim analysis, this trial had to be closed earlier than planned, based on the significantly positive results noted with the combination regimen. The median overall survival for patients in the FOLFIRINOX was 11.1 months compared with 6.8 months for those receiving single agent GEMZAR®. At one year, 48% of patients in the FOLFIRINOX group were alive compared to 20% for those in the GEMZAR® group. The median progression free survival was 6.4 months for the patients treated with FOLFIRINOX compared to 3.3 months for those treated with single agent GEMZAR®. Quality of life was also superior in the FOLFIRINOX group compared to those who were treated with GEMZAR®. For the very first time, we now have a combination chemotherapy regimen for advanced pancreatic cancer that confers survival benefit. J Clin Oncol 28:303s, 2010 (suppl; abstr 4010)

Improving Survival in Metastatic Pancreatic Cancer

A combination of Oxaliplatin, Irinotecan, Fluorouracil and Leucovorin (FOLFIRINOX) chemotherapy given to individuals with metastatic pancreatic cancer resulted in superior Response Rates, Progression Free Survival and Overall Survival compared to single agent Gemcitabine. For the first time, we now have a regimen that has demonstrated survival benefit for this hard-to-treat cancer.

This data was presented at the 2010 ASCO meeting

GVAX – Vaccine for Pancreatic Cancer

GVAX is a therapeutic cancer vaccine, developed to induce antitumor immunity. Traditional vaccination against specific bacterial and viral infections involves the injection of the specific weakened bacteria/virus or a structural component of the bacteria or virus. The body then mounts an immune response and is ready to respond to an infection associated with that specific bacteria or virus.

Based on the same principle GVAX, a cancer vaccine, comprises of patient derived tumor cells, that are irradiated to prevent it from dividing and is then genetically modified to secrete GM-CSF (Granulocyte Macrophage Colony Stimulating Factor). GM-CSF is important for the growth and activation of dendritic cells also known as Antigen Presenting Cells. This vaccine when injected activates the dendritic cells, which in turn stimulates the patients immune system to attack the vaccine tumor cells, which are in fact similar to the patients original tumor cells. This vaccine therefore theoretically boosts the body’s immune system to fight the patients tumor, without causing collateral damage.

The FDA granted Orphan Drug Status for GVAX vaccine to treat pancreatic cancer. An orphan drug is an agent developed to treat a rare medical disorder affecting fewer than 200,000 people in the United States.

GVAX vaccine is being studied in other types of cancer as well. It should however be noted that vaccines by themselves may be of benefit only for patients with low volume disease with adequately functioning immune system.

Everolimus for Neuroendocrine Tumors

In the RADIANT-2 trial, Everolimus (Afinitor), an oral mTOR (mammalian Target Of Rapamycin) inhibitor was administered in combination with Octreotide LAR to patients with advanced non pancreatic neuroendocrine tumors. The control group received placebo in combination with Octreotide LAR. There was a significant improvement in the progression free survival in favor of the mTOR inhibitor given in combination with Octreotide LAR.

We now have a viable treatment option for the treatment of carcinoid tumors with symptoms.