Henry Q. Xiong, MD, PhD

Question: What’s the new drug available for  pancreatic cancer and what other treatments are being tested?

 Pancreatic cancer accounts for only about  2 percent of the nation’s new cancer cases, but as the fourth deadliest cancer,  new treatments have been desperately needed to combat the disease. After meeting  the goal of improving survival, the Food and Drug Administration approved  Tarceva (erlotinib) in late 2005 for first-line treatment of advanced  pancreatic cancer in combination with Gemzar (gemcitabine). Already approved to  treat lung cancer, Tarceva is an oral agent that suppresses cancer cell growth  by inhibiting the function of a cell surface protein called the epidermal growth  factor receptor, or EGFR.

The phase III study that led to the drug’s approval in pancreatic cancer  compared Gemzar plus Tarceva with Gemzar alone in patients who had not received  previous chemotherapy. The study found that 24 percent of patients who received  the drug combination were alive at one year compared with 17 percent who  received only Gemzar. The improvement, although small, was statistically  significant and indicates the difference did not occur by chance. In addition,  patients who received Tarceva had improved progression-free survival (3.8  months) compared with those who did not receive the drug (3.5 months). Side  effects of Tarceva were tolerable and included skin rash and diarrhea.

The study was the first to show a survival advantage with an EGFR inhibitor  in pancreatic cancer. It is a welcome addition for patients whose treatment  options remain very limited. However, one has to remember that the improvement  was disappointingly small. Such an incremental improvement indicates that only a  minority of patients may benefit from Tarceva. Therefore, patients should  discuss the potential benefits and side effects of the drug with their  physicians.

Two molecularly targeted agents approved for treating colorectal cancer,  Erbitux (cetuximab) and Avastin (bevacizumab), are currently under  investigation in combination with Gemzar for patients with advanced pancreatic  cancer. Erbitux, an antibody that binds to EGFR to stop cancer growth, has shown  promising activity against pancreatic cancer in an ongoing phase II trial in  combination with Gemzar. Also impressive is the activity of Avastin in treating  pancreatic cancer. The targeted agent inhibits new blood vessel formation by  preventing the binding of the vascular endothelial growth factor to its  receptor. A phase III trial comparing Avastin plus Gemzar with Gemzar alone is  currently ongoing. With final results expected within the next two years, these  studies will define the usefulness of Erbitux and Avastin for advanced  pancreatic cancer.

Two European trials have tested the impact of Xeloda (capecitabine), a drug  approved for certain types of breast and colon cancers, on advanced pancreatic  cancer. One of these studies found that although Xeloda plus Gemzar did not  improve overall survival compared with Gemzar alone, a subgroup analysis of  patients with a good performance status (patients who were better able to  withstand aggressive treatment) who received the combined therapy showed a  2.6-month improvement in median overall survival. A similarly designed trial in  the United Kingdom reported a statistically significant improvement of overall  survival (7.4 versus six months) in patients who received Xeloda plus Gemzar  compared with those who received Gemzar alone. These studies demonstrated that  the Xeloda combination is effective in pancreatic cancer, especially for  patients with higher performance status scores.

Another drug used to treat colon cancer may have activity in pancreatic  cancer. A phase III trial of Eloxatin (oxaliplatin) plus Gemzar compared with  Gemzar alone showed an improvement of the response rate and the progression-free  survival in patients who received the drug combination. However, the improvement  of overall survival was not statistically significant. Another phase III trial  is under way that will compare Eloxatin plus Gemzar with Gemzar alone given as  either prolonged or standard transfusion. Data from this trial will hopefully  demonstrate any overall survival advantage for the Eloxatin/Gemzar regimen.

As treatment research continues, scientists also continue in their efforts to  better understand the causes of pancreatic cancer and improving the ability to  detect tumors of the pancreas at earlier stages.

Articles

The new drug for pancreatic cancer and other treatments being tested.

Henry Q. Xiong, MD, PhD

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