Stage IV

Pancreatic Cancer

Pancreatic cancer is considered stage IV if it has spread to distant locations in the body, such as the liver, lungs, or adjacent organs including the stomach, spleen, and/or the bowel. Sometimes it can only be determined that a pancreatic cancer is in stage IV once surgery is completed.

Stage IV Pancreatic Cancer is Broadly Divided into Two Groups:

  • Stage IVA pancreatic cancer is locally confined, but involves adjacent organs or blood vessels, thereby hindering surgical removal. Stage IVA pancreatic cancer is also referred to as localized or locally advanced.
  • Stage IVB pancreatic cancer has spread to distant organs, most commonly the liver. Stage IVB pancreatic cancer is also called metastatic. The goal of treatment for patients with localized IVA disease is to induce a remission, or a disease-free period that may last months or years. Management of patients with Stage IVB disease is often aimed at controlling symptoms and pain from the cancer.

Treatment of Localized Stage IVA Pancreatic Cancer

Pancreatic cancer is often not diagnosed until it is in Stage IVA, meaning the cancer has invaded adjacent organs or major blood vessels. When this occurs surgical removal of the cancer (which provides a chance at long-term cure) is seldom an option. Therefore, the goal of treatment of patients with Stage IVA pancreatic cancer is to induce a remission, which is a cancer-free period that may last months or years, and to prevent and control symptoms.

Treatment for Stage IVA pancreatic cancer may include palliative surgery, and systemic chemotherapy, or chemoradiation, which is chemotherapy and radiation delivered together.  Occasionally, a surgical bypass procedure may be performed to alleviate complications of the cancer, such as jaundice, intestinal obstruction, or pain, thereby improving quality of life.

Treatment of Non-localized Stage IVB (Metastatic) Pancreatic Cancer

The majority of patients with Stage IV cancer have metastatic disease (Stage IVB), which means that cancer has spread to distant locations in the body that often include the liver and other areas of the abdominal cavity. To kill cancer cells that have spread throughout the body, a systemic treatment is necessary, and this is typically chemotherapy.

Historically, patients with metastatic pancreatic cancer have been considered incurable and rarely survived more than one year. However, with newer treatments, some patients are surviving 1-2 years and can experience improved quality of life. In addition, the management of patients with Stage IV pancreatic cancer is focused on reducing pain and maintaining nutrition. Pain relief can be achieved by destroying the nerves that provide sensation in the area around the pancreas. This is usually performed by injection of alcohol or other chemicals either through the skin or during an open abdominal operation.

Chemotherapy

Chemotherapy is any treatment involving the use of drugs to kill cancer cells.  Cancer chemotherapy may consist of single drugs or combinations of drugs and can be administered through a vein or delivered orally in the form of a pill.  Chemotherapy is considered a systemic therapy because the drugs circulate throughout the body and can kill cancer cells that have spread to locations distant from where the cancer started. Chemotherapy is commonly used to treat both locally advanced (Stage IVA) and metastatic (Stage IVB) pancreatic cancer.

Gemzar® (gemcitabine): The standard  treatment of stage IV pancreatic cancer is systemic therapy with Gemzar® based chemotherapy or participation in a clinical trial evaluating new chemotherapy or precision cancer medicines.1,2

Chemoradiation Therapy

Combining chemotherapy with radiation therapy, a technique called chemoradiation, may provide more benefit than chemotherapy alone for some patients with Stage IVA pancreatic cancer,3 but is not typically a treatment for patients with Stage IVB disease.

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. Areas of active investigation aimed at improving the treatment of pancreatic cancer include 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.4,5 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.6 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%.

Immunotherapy-Trials in Humans Coming

A new study in mice by researchers at Fred Hutchinson Cancer Research Center has found that a specialized type of immunotherapy — even when used without chemotherapy or radiation — can boost survival from pancreatic cancer, a nearly almost-lethal disease, by more than 75 percent. The findings are so promising that human clinical trials are now ongoing.

The researchers devised a therapy using T cells, disease-fighting immune cells, that they engineered in the lab to recognize and attack pancreatic cancer.  T cells — engineered to recognize and kill cells bearing a protein called mesothelin, which is overproduced by virtually all pancreatic tumors get into the mice’s tumors and started attacking them.7

Phase I Clinical Trials

New chemotherapy drugs continue to be developed and evaluated in patients with advanced cancers in Phase I clinical trials. The purpose of Phase I trials is to evaluate new drugs in order to determine the safety and tolerability of a drug and the best way of administering the drug to patients.

Next: Surgery for Pancreatic Cancer

References


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 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.

4 http://news.cancerconnect.com/preliminary-results-suggest-that-pamrevlumab-is-promising-in-pancreatic-cancer/

5 http://news.cancerconnect.com/larotrectinib-demonstrates-76-percent-response-rate-trk-fusion-cancers-including-pancreatic-cancer/

6 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

7 https://www.fredhutch.org/en/news/releases/2015/10/immunotherapy-for-pancreatic-cancer-boosts-survival-in-mice.html