Optimizing Adjuvant Therapy for Resected Pancreatic Cancer
Name of the Trial
Phase III Randomized Study of Adjuvant Gemcitabine Hydrochloride with Versus Without Erlotinib Hydrochloride Followed by the Same Chemotherapy Regimen With Versus Without Chemoradiotherapy With Either Capecitabine or Fluorouracil in Patients With Resected Head of Pancreas Adenocarcinoma (RTOG-0848). See the protocol summary.
Dr. Ross Abrams, Radiation Therapy Oncology Group
Why This Trial Is Important
Pancreatic adenocarcinoma is the fourth leading cause of cancer death in the United States. It develops in the lining of ducts in the pancreas that deliver digestive juices to the small intestine through the main pancreatic duct. The majority of pancreatic adenocarcinomas occur in the head of the pancreas, the part of the organ that is closest to the small intestine.
The only potentially curative treatment for pancreatic adenocarcinoma is a complex surgical procedure called the Whipple procedure. However, most patients are not eligible for this treatment because the cancer has spread beyond the pancreas by the time it is diagnosed. Furthermore, about 80 percent of those who have the Whipple procedure relapse and die within 5 years due to the presence of microscopic deposits of tumor cells that remain behind after surgery. Consequently, doctors often use adjuvant therapies to try to destroy the remaining cancer cells.
Chemoradiotherapy that includes a radiosensitizing agent, such as 5-fluorouracil (5-FU), is often used as adjuvant treatment for surgically resected pancreatic cancer. More recently, adjuvant chemotherapy with the drug gemcitabine has been shown to delay recurrence and modestly improve survival. Doctors are now investigating whether combining these adjuvant therapies can further increase survival after surgery. Additionally, they want to know if adding a second drug to gemcitabine will improve survival compared with gemcitabine alone. In patients with advanced, inoperable pancreatic cancer, the drug erlotinib has shown the ability to prolong survival when combined with gemcitabine. Therefore, doctors are hopeful it will also help patients who have had surgery.
In this clinical trial, patients with resected adenocarcinoma of the head of the pancreas will be randomly assigned to receive either gemcitabine for 5 treatment cycles or gemcitabine and erlotinib for 5 cycles. Patients who do not experience disease progression (recurrence or growth of residual tumor tissue) will then be randomly assigned to undergo an additional cycle of the same chemotherapy regimen with or without subsequent chemoradiation using either intravenous 5-FU or a similar oral drug called capecitabine. Doctors will follow the patients’ survival, compare the toxicity of these treatments, and try to determine whether certain biological characteristics of the patients are associated with outcomes.
“This trial is basically asking two questions,” said Dr. Abrams. “The first question is, do patients treated with gemcitabine and erlotinib do better than those treated with gemcitabine alone? The second question is, for those patients who finish chemotherapy without evidence of recurrence or progression, does the addition of radiation to the area where the tumor was removed, along with 5-FU or capecitabine, accomplish something above and beyond the chemotherapy?”