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

Answer: 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.

—Henry Q. Xiong, MD, PhD, is an assistant professor in the department of gastrointestinal medical oncology at M.D. Anderson Cancer Center