When pancreatic cancer has returned following initial treatment, it is referred to as recurrent or relapsed cancer. Recurrent pancreatic cancer is very difficult to treat and treatment options are limited.

Some patients are offered treatment with chemotherapy for the purpose of prolonging their duration of survival and alleviating symptoms from progressive cancer. Most patients with recurrent pancreatic cancer have already received 5-fluouracil or Gemzar®-based chemotherapy . Once a patient's cancer has returned after being treated with chemotherapy, the ability of other chemotherapy drugs to kill the cancer cells is disappointingly low. Therefore, many patients with recurrent pancreatic cancer are offered therapies aimed at palliation, or relief of the uncomfortable side effects of their cancer and/or cancer treatment. This approach is sometimes called supportive care. Pain relief can be achieved by destroying the nerves that provide sensation from the area around the pancreas. This is usually performed by injection of alcohol or other chemicals during an open abdominal operation or via a skin injection.

The following is a general overview of treatment for recurrent pancreatic cancer. Circumstances unique to each patient's situation may influence how these general treatment principles are applied and whether the patient decides to receive treatment. The potential benefits of receiving treatment, no treatment, supportive care, or participating in a clinical trial must be carefully balanced with the potential risks. The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer 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. Future progress in the treatment of recurrent pancreatic cancer will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active exploration to improve the treatment of recurrent pancreatic cancer include the following:

Biological therapy

Biological therapies are naturally occurring or synthesized substances that direct, facilitate, or enhance the body's normal immune defenses. Biologic therapies include interferons, interleukins, monoclonal antibodies, vaccines, and other compounds. Monoclonal antibodies are proteins that can be made in the laboratory and are designed to recognize and bind to very specific sites on a cell. This binding action promotes anti-cancer benefits by eliminating the stimulating effects of growth factors and by stimulating the immune system to attack and kill the cancer cells to which the monoclonal antibody is bound. In an attempt to improve survival rates, the following biological therapies are being tested alone or in combination with chemotherapy in clinical trials:

Erbitux™: Erbitux™ is a monoclonal antibody, which is a protein that has been manufactured in a laboratory to bind to specific sites on cancer cells. Erbitux™ binds to the epidermal growth factor receptor (EGFR) so that growth factors are unable to bind to EGFR. This ultimately slows or stops the growth process of cancer cells that express EGFR on their surface. In addition, Erbitux™ appears to augment anti-cancer activity of chemotherapy agents through biological processes not yet understood. Erbitux™ was FDA-approved for the treatment of colon cancer in February 2004.

Researchers from the M.D. Anderson Cancer Center have reported that the addition of Erbitux™ to Gemzar® may improve survival for patients with advanced pancreatic cancer. This trial involved 40 patients with advanced pancreatic cancer who had tested positive for overexpression of EGFR. Results indicate that more of the patients who received Gemzar® plus Erbitux™ lived one year or more and were cancer-free for longer than the patients who were treated with Gemzar® alone

Virulizin®: Virulizin® is a biological therapy that activates the body's own immune system to recognize and eliminate cancer cells. The exact mechanism that Virulizin® works has not been identified with certainty. However, researchers think that it induces apoptosis (cell death) of cancer cells by stimulating the release of tumor necrosis factor and stimulating macrophages, the clean-up cells of the immune system.

Three of the early studies conducted with Virulizin® involved the treatment of patients with pancreatic adenocarcinoma. The majority of patients participating in these studies were those who had failed conventional treatment including surgery or chemotherapy. Disease stabilisation was observed in patients treated with Virulizin®, and based on a combined analysis of the data from these three studies, the survival of the patients treated with Virulizin® was better than a similar patient population receiving a standard chemotherapy drugs.

Virulizin® was granted “fast track” status by the FDA. Fast-track status expedites the review and approval process of an agent that is intended for life-threatening diseases. The phase III clinical trial, which is the last trial prior to FDA approval, involves patients with advanced pancreatic cancer who will receive treatment with either Gemzar ® alone or Gemzar® plus Virulizin®.

Herceptin®: Herceptin® is another monoclonal antibody that binds to HER2 receptor, which is a protein on the surface of some cancer cells. This binding action promotes anti-cancer benefits through two distinct processes. First, the binding of Herceptin® blocks growth factors by binding to HER2, thereby eliminating their stimulating effects on cancer cells. Second, the binding action of Herceptin® appears to stimulate the immune system to attack and kill the cancer cells to which Herceptin® is bound.

Researchers from Brown University have found that treatment of patients with advanced pancreatic cancers that overexpress HER2 with Gemzar® plus Herceptin® appears to produce longer survival than treatment with Gemzar® alone. Approximately 72% of patients treated with the combination demonstrated an anti-cancer response. Approximately 24% of patients lived one year or more following treatment.

Advances in Chemotherapy

Chemotherapy involves the use of anti-cancer drugs to destroy cancer cells throughout the body. Chemotherapy is considered a systemic therapy because the drug circulates throughout the body and can kill cancer cells that have spread to locations distant from where the cancer started. Researchers continue to evaluate new chemotherapy drugs and combinations of drugs.

Gemzar®: The standard chemotherapy drug for the treatment of advanced pancreatic cancer is Gemzar®, which has been shown to improve response to treatment, time to cancer progression, and survival duration when compared with the older chemotherapy drug 5-fluorouracil. Results from one clinical trial indicate that Gemzar® therapy in patients with recurrent pancreatic cancer helped patients to feel better and require less pain medication. The patients in this trial had cancer that continued to grow despite treatment with 5-fluourauracil. Although the quality of life may be improved with chemotherapy, the duration of survival has not been improved over palliative care, also called supportive care.

Combination chemotherapy (regimens): Combinations of chemotherapy drugs, called regimens, may produce more anti-cancer response than treatment with just one drug. Regimens that combine Gemzar® with other chemotherapy drugs are being evaluated in patients with advanced pancreatic cancer.

Gene Therapy

Currently, there are no gene therapies approved for the treatment of pancreatic cancer. Gene therapy is defined as the transfer of new genetic material into a cell for therapeutic benefit. This can be accomplished by replacing or inactivating a dysfunctional gene or replacing or adding a functional gene into a cell to make it function normally. A few gene therapy studies are being carried out in patients with advanced pancreatic cancer. If successful, these therapies could be applied to patients with earlier stage disease.

ONYX-015: ONYX-015 is one type of gene therapy that has been investigated in pancreatic cancer. ONYX-015 is a genetically engineered, or altered, adenovirus—a virus that causes a common cold. This virus has been altered in such a way that it will infect and kill cancer cells with a mutated p53 gene, but will not kill normal healthy cells. Many different types of cancers develop due to a mutation (alteration) in a certain gene called the p53 gene, which is the gene responsible for regulating normal cell death. ONYX-015 was developed to specifically target and infect cells with a destroyed or mutated p53 gene.

Researchers from UCLA recently conducted a clinical trial evaluating the effectiveness and tolerability of injections of ONYX-015 plus the chemotherapy agent Gemzar® in the treatment of 21 patients with inoperable pancreatic cancer that had spread either locally or to distant sites in the body. The injections were guided by ultrasound and delivered directly into the areas of cancer in the pancreas. Anti-cancer responses or stabilization of cancer was achieved in nearly 50% (10) of patients, while 11 patients had cancer progression or could not tolerate therapy

Managing Side Effects

Managing the side effects of cancer and/or cancer treatment is an important part of receiving optimal care. Side effects cause inconvenience, discomfort, and may occasionally be fatal. Additionally and perhaps more importantly, side effects may prevent doctors from delivering the prescribed dose of therapy at the specific time and schedule of the treatment plan. Because the expected outcome from therapy is based on delivering treatment at the dose and schedule prescribed in the treatment plan, a change from the treatment plan may reduce your chance of achieving an optimal outcome. This is extremely important to understand. In other words, side effects not only cause discomfort and unpleasantness, but may also compromise your chance of cure by preventing the delivery of therapy at its optimal dose and time. For more information, go the Managing Side Effects section.

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.