Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor updated 10/2020
Stage I-II pancreatic cancer, refers to cancer that is confined to the pancreas, does not involve any adjacent organs, has not spread to any of the local lymph nodes and cannot be detected in other locations in the body.
Currently treatment for stage I-II adenocarcinoma of the pancreas is surgical removal of the cancer. The most common surgical procedure is a pancreaticoduodenectomy, or Whipple procedure, which involves removal of a portion of the pancreas, small intestine (duodenum), and stomach, as well as the entire gallbladder. The exact surgical procedure may differ based on the location and extent of the cancer within the pancreas.
Despite undergoing surgical removal of all visible cancer, a majority of patients will experience a recurrence of their cancer because prior to surgery a small amount of cancer spread outside the pancreas and therefore, was not removed by surgery. It is necessary to develop effective systemic treatments that can find and destroy cancer cells anywhere in the body in order to reduce the risk of cancer recurrence.1
Systemic Therapy: Precision Cancer Medicines, Chemotherapy, and Immunotherapy
Systemic therapy is treatment directed at destroying cancer cells throughout the body. Because patients with pancreatic cancer have small amounts of cancer that have spread away from the pancreas, an effective systemic treatment is needed to cleanse the body of these cells in order to prolong survival and improve the chance of cure.
Systemic treatment can be administered after surgery (adjuvant therapy) or before surgery (neoadjuvant therapy). Systemic therapy may include chemotherapy, precision cancer medicines, immunotherapy or a combination of these therapies.2,3
Historically a combination of chemotherapy drugs consisting of Gemzar (gemcitabine) plus Xeloda (capecitabine) was the most widely recommended standard therapy but recent clinical trials suggest the chemotherapy regimen know as mFOLFIRINOX is superior.
A large clinical trial in individuals with stage I-III non-metastatic pancreatic adenocarcinoma who had all visible tumor surgically removed were treated with the standard chemotherapy drug Gemzar or a more aggressive multi-drug treatment regimen mFOLFIRINOX for 6 months and directly compared.4,5
At a median follow-up of 33.6 months from the treatment individuals treated with mFOLFIRINOX survived without evidence of cancer an average of 21.6 months compared to only 12.8 months for Gemzar treated patients. The median overall survival was also improved; 54.4 months for mFOLFIRINOX versus 35.0 months for Gemzar.
A subsequent clinical trial known as ESPAC-4 has also shown that 5-year survival rates are improved to 28% with adjuvant Gemzar plus Xeloda versus 20% with Gemzar alone.10
Doublet therapy with Gemzar and Xeloda or monotherapy with Gemzar alone or fluorouracil plus folinic acid alone can also be offered as an alternative.
Understanding DNA Damage Response or DDR and Cancer Treatment
What is DNA Damage Response or DDR?
Radiation therapy, or radiotherapy, uses high-energy rays to damage or kill cancer cells by preventing them from growing and dividing. Similar to surgery, radiation therapy is a local treatment used to eliminate or eradicate visible cancers. Radiation therapy is not useful in eradicating cancer cells that have already spread to other parts of the body. It is particularly effective as an adjuvant therapy (therapy given in addition to the primary treatment) to surgery by helping to eliminate any microscopic cancer cells leftover after surgery. Clinical studies that have evaluated adjuvant radiation therapy have yielded conflicting results and there currently remains no consensus whether radiation should be used as adjuvant therapy or combined with chemotherapy for the treatment of pancreatic cancer although it is offered to many patients.(6) Patients should clearly understand the risks and benefits of being treated with radiation and discuss them with their physician.
Strategies to Improve Treatment
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies.
Development of Precision Cancer Medicines: The precision caner medicine Lynparza (olaparib) has been demonstrated to improve treatment outcomes in patients with a specific genetic mutuation known as BRCA. All patients should be tested for BRCA and other genomic biomarkers to determine if they are eligible to participate in clinical trials of new precision cancer medicines.7
Research is ongoing to develop new precision medications that specifically target cancer cells. These trials require a sample of the cancer or liquid biopsy to be available in order to evaluate for biomarkers. Patients should learn about options to participate in these trials prior to surgery in order to ensure that cancer tissue is obtained correctly. Learn more about development of precision cancer medicines for treatment of pancreatic cancer.
Vaccines: A vaccine is a form of immunotherapy that is designed to help the patient’s immune system destroy the cancer by activating the patient’s immune cells against the cancer. Vaccines are made from a variety of substances that often include the actual cancer cells removed from the patient. A difficulty in preparing vaccines is that the patient’s cancer cells must be processed immediately following surgery. Patients and their surgeon must therefore prepare in advance to ensure the removed cancer cells can be handled properly for vaccine preparation. Vaccines are currently being evaluated in clinical studies.
The GVAX vaccine has been designed to stimulate the immune system to fight pancreatic cancer.8 The vaccine is comprised of radiated pancreatic cancer cells that are not able to replicate or grow. The cells have been modified to secrete a substance referred to as granulocyte macrophage colony stimulating factor (GM-CSF), which stimulates the immune system to recognize pancreatic cancer cells and attack them.
Results from the initial trial evaluating the GVAX vaccine are promising and additional clinical trials are ongoing.
At a median follow-up of 32 months:
- Survival at one year was 88%.
- Survival at two years was 76%.
Neoadjuvant Therapy: In an effort to increase the chance that a cancer may be surgically removed, some cancer centers use radiation therapy and chemotherapy before surgery to shrink the cancer. The use of treatment before surgery is referred to as “neoadjuvant therapy.” In addition to potentially shrinking the cancer so that it can be removed, neoadjuvant therapy allows patients to avoid the difficulty of undergoing treatments after surgery, which is a time when they may be experiencing side effects. Approximately 25% to 33% of patients are unable to receive chemotherapy or radiation treatment following surgery.
A treatment plan that includes neoadjuvant therapy guarantees that systemic therapy is delivered immediately, which may increase the chance of eradicating small amounts of cancer that may have already spread to distant locations in the body and cannot be removed by surgery. Clinical trials are ongoing to evaluate neoadjuvant chemotherapy administered alone or in combination with adjuvant therapy, and the results of some small studies suggest that neoadjuvant therapy may improve survival.9
- National failure to operate on early stage pancreatic cancer. Annals of Surgery. 2007;246:173-180.
- Oettle H, Neuhaus P. Adjuvant therapy in pancreatic cancer: a critical appraisal. Drugs. 2007;67:2293-310.
- Neoptolemos J, Palmer D, Ghaneh P, et al. ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma. J Clin Oncol 34, 2016 (suppl; abstr LBA4006)
- American Society of Clinical Oncology (ASCO) 2018 Annual Meeting. Presented June 4, 2018. Abstract LBA4001
- Hazard L, Tward JD, Szabo A, Shrieve DC. Radiation therapy is associated with improved survival in patients with pancreatic adenocarcinoma: results of a study from the Surveillance, Epidemiology, and End Results (SEER) registry data. Cancer. 2007;110:2191-201.
- Laheru D, et al. A Safety and Efficacy Trial of Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected with the GM-CSF Gene in Combination with Adjuvant Chemotherapy for the Treatment of Adenocarcinoma of the Pancreas. Proceedings from the International Conference of AACR-NCI-EORTC. November, 2005. Philadelphia, PA. Abstract #C28
- Takai S, Satoi S, Yanagimoto H et al. Neoadjuvant chemoradiation in patients with potentially resectable pancreatic cancer. Pancreas. 2008 Jan;36(1):e26-32.
- Neoptolemos J P, Palmer D H, Ghaneh P, et al. ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma: Five year follow-up. Presented at: the 2020 ASCO Annual Meeting; May 29-31, 2020. Abstract 4516.