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
A combination of chemotherapy drugs consisting of Gemzar (gemcitabine) plus Xeloda (capecitabine) is the most widely recommended standard therapy because the combination has an improved response rate and 5 year survival without a concomitant increase in side effects.3
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.4 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. In addition to continued development of chemotherapy treatment regimens active investigation aimed at improving the treatment of early stage pancreatic cancer includes the following:
Development of Precision Cancer Medicines: Research is ongoing to develop new medications that specifically target cancer cells in clinical trials. These trials typically 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.
Germline BRCA – mutated pancreatic cancer can be treated with a precision cancer medicine known as a PARP inhibitor. BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA. When either of these genes is mutated, or altered DNA damage may not be repaired properly, and the cells are more likely to develop additional genetic alterations that can lead to cancer.5,6
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.7
1 National failure to operate on early stage pancreatic cancer. Annals of Surgery. 2007;246:173-180.
2 Oettle H, Neuhaus P. Adjuvant therapy in pancreatic cancer: a critical appraisal.Drugs. 2007;67:2293-310.
3 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)
4 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.
5 Pancreatic Cancer Action. Facts and statistics. Accessed February 2019 from https://pancreaticcanceraction.org/about-pancreatic-cancer/medical-professionals/stats-facts/facts-and-statistics/
7 Takai S, Satoi S, Yanagimoto H et al. Neoadjuvant chemoradiation in patients with potentially resectable pancreatic cancer. Pancreas. 2008 Jan;36(1):e26-32.
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