Systemic Therapy for Pancreatic Cancer
For decades the chemotherapy of pancreatic cancer consisted of 5-fluorouracil-based regimens. Despite apparent improvements in response rates reported in small pilot studies with combination regimens, no clear superiority over single-agent 5-FU was demonstrated until recently. Recent trials in patients with metastatic disease have shown that palliative chemotherapy using gemcitabine produced similar clinical activity to 5-FU, with improved patient quality-of-life. The addition of the oral biologic agent erlotinib to gemcitabine resulted in a modest improvement in median survival. Both of these agents are FDA-approved for the treatment of pancreatic cancer. Because of the low response rates to chemotherapy in pancreatic cancer compared to chemotherapy for many other types of cancer, there are a multitude of ongoing clinical trials which study the potential utility of newer pharmacologic agents.
Specific Situations Where Chemotherapy is Considered Include:
Patients who have undergone surgical resection: Because of the high risk of recurrence even in patients who successfully undergo surgery for pancreas cancer with negative surgical margins, the addition of postoperative chemotherapy and/or radiation therapy is supported by several generations of clinical trials. The most standard approach has been to combine an extended (6 months or longer) period of chemotherapy in an attempt to eradicate micrometastatic disease, with chemotherapy given concurrently with radiation therapy to potentiate the effects of radiation on any subclinical residual disease in the tumor bed. The extended chemotherapy component currently used would most commonly be gemcitabine, with 5-FU given concurrently with RT. This approach appears to improve longterm survival by approximately 10-15%. More recently, comparable results have been obtained with a program that includes 6 months of gemcitabine therapy without the radiation therapy component.
Patients with locally advanced but unresectable disease: The anatomic location of pancreatic cancer often makes resection impossible due to the involvement of major blood vessels, and some patients with localized disease are not candidates for surgery because of their overall medical condition. These patients can be treated either with chemotherapy alone in an attempt to control the localized disease and hopefully delay the progression to metastatic disease, or with a combination of chemotherapy and radiation therapy. Although local control of the disease is often achieved, a large majority of these patients ultimately die from progressive cancer.
Patients whose tumor is borderline-resectable who have the potential to be treated with an aggressive combined-modality approach: Patients whose disease is extensive enough on imaging studies that they are close to standard criteria for unresectability can be treated with “neoadjuvant” chemoradiotherapy preoperatively, in an attempt to reduce the tumor size and make them more clearly resectable. Although this approach can render some patients resectable, it remains unclear whether this results in sufficient benefit in the chances of survival to be worth the significant risk of toxicity, and its use is limited to highly selected patients.
Patients with metastatic disease: In these incurable patients, chemotherapy can be considered as part of an overall treatment plan which seeks to maximize time of survival and minimize toxicity. Choice of treatments needs to be individualized depending on the patient’s medical and psychosocial condition. Standard therapy consists of intravenous gemcitabine on a weekly schedule, with or without the addition of oral erlotinib. Once therapy is initiated, patients should be closely monitored for the potential of changing therapy depending on whether or not the disease is progressing and on the toxicity profile of the regimen.