Chemotherapy for Pancreatic Cancer: State of the Union

Medical oncologists, specialists in treating cancer with chemotherapy, play a vital role in the care of patients with pancreatic cancer. Most will need chemotherapy at some point during their care, either before surgery, after surgery, or as a primary treatment for tumors that are not operable. Although many people fear chemotherapy, it can improve patients’ symptoms and quality of life, and prolong survival. Yet much work remains to get better results for patients with pancreatic cancer, says Paul Oberstein, MD, medical oncologist at the Pancreas Center. In the following interview, Dr. Oberstein discusses the latest advances in chemotherapy for pancreatic cancer and why he is optimistic.

What is your role at the Pancreas Center?

Dr. Oberstein: I am part of the multidisciplinary team that determines the sequence of when patients should have chemotherapy, radiation, and surgery, and I oversee the patient’s chemotherapy treatment plan. I often work with patients after surgery, but in some cases I treat patients to shrink their tumors so that they become operable.

In addition to treating patients, I conduct translational research in the Olive Laboratory in the Herbert Irving Comprehensive Cancer Center. That research involves identifying new chemotherapy agents in animal subjects with the goal of bringing the most promising agents forward as clinical trials for our patients.

What chemotherapy options are currently available for patients with advanced pancreatic cancer?

Dr. Oberstein: Only a few drugs have been proven to be effective in advanced pancreatic cancer, and most patients receive chemotherapy combinations that are based on gemcitabine (Gemzar) which has long been known to be effective in this disease. Regimens consisting of combinations of several chemotherapeutic agents are often more effective than the drugs used singly. One particularly promising three-drug regimen consists of gemcitabine, docetaxel  (Taxotere), and capecitabine (Xeloda), together known as GTX. This regimen was developed by oncologists at the Pancreas Center and has been used widely for the last decade. A recent large clinical trial clearly demonstrated the benefit of using combination therapy with gemcitabine and nab-paclitaxel (Abraxane) for patients with metastatic disease. This trial led to FDA approval of Abraxane in combination with gemcitabine in September 2013, and this agent has already had a large impact on the treatment of our patients in The Pancreas Center.

How significant is this improvement for patients?

Dr. Oberstein: Unfortunately, even with newer regimens the median survival for patients with advanced pancreatic cancer is less than a year. However after many attempts we finally have clear evidence from advanced clinical trials that both gemcitabine/nab-paclitaxel and another combination regimen called FOLFIRINOX provide robust benefits in shrinking tumors and prolonging survival. The significance is that it represents a robust incremental benefit. Each incremental benefit allows us to build further and find increasingly active combinations of therapies. This is the model that has proven successful in treating other common cancers. So although these incremental benefits are not a cure, they are exciting because we have a platform from which to build further.

What are your next steps in researching better options?

Dr. Oberstein: Our ultimate goal is to shrink tumors, improve patients’ quality of life, and improve survival. Right now we have several good options for patients: each regimen combines drugs with different mechanisms of action, side effects, tolerability, and involve different time commitments for treatment. Our multidisciplinary team (surgeons, medical oncologists, pathologist, radiologist, the palliative care team, and nutritionist) reviews each patient’s case to determine what may be most appropriate given his or her case.

The choice of which to use depends on the person’s overall picture, what they can tolerate, and other factors. But no current therapy is fully sufficient and many questions remain to be answered. Continued studies aim to better identify which drugs or combinations will benefit which patients. We also need to research genetic factors associated with pancreatic cancer and their impact on the efficacy of therapies. Toward this end, the Pancreas Center has several initiatives collecting tumor samples from patients, which will be used in such studies.

One of the most important methods for improving outcomes for patients involves conducting well designed clinical trials. Starting this winter, the Pancreas Center will be participating in a new national study of an investigational drug that may build on recent advances. In this study all patients will receive gemcitabine and nab-paclitaxel, and half will receive the investigational drug called PEGPH20 which is thought to work by breaking down the cells that surround the tumor. By comparing outcomes among the patients who did and did not receive PEGPH20, the study will assess the efficacy of this approach in treating pancreatic cancer. We have begun screening patients with metastatic pancreatic cancer and expect to begin enrolling our first patients very soon.

Why are you optimistic about what has long been a sobering field of research and care?

Dr. Oberstein: The science of pancreatic cancer treatment has been growing for decades but recent clinical advances are gaining significant momentum.  The need for new therapies is very high and this is a very meaningful field. We have a long way to go, but I am excited to be part of research efforts that will hopefully build on recent advances to make even greater gains for treating our patients. We have reason to anticipate improved outcomes across a broad range of patients with pancreatic cancer in the coming years.