A recent study published in the Journal of Clinical Oncology has found that people with early-stage pancreatic cancer treated with chemoradiation therapy before surgery lived substantially longer than people who underwent surgery first. The study was comprised of results from two clinical trials and used data from pancreatic cancer patients over nearly five years. The results are expected to improve the outlook for people diagnosed with early-stage pancreatic cancer that can be treated with surgery.
To better understand the implications of the study, it’s first important to understand what chemoradiation therapy is, and how it can help early-stage pancreatic cancer patients.
What Is Chemoradiation Therapy?
Chemoradiation therapy is a type of cancer treatment that involves having chemotherapy and radiotherapy at the same time. Chemotherapy uses anti-cancer (cytotoxic) drugs to destroy cancer cells. Radiotherapy utilizes high-energy waves, such as x-rays, to destroy or damage cancer cells. The drugs used in chemotherapy can make cancer cells more susceptible to radiotherapy treatment. This means that combining both treatments can be more effective than having either treatment on its own.
Combining chemotherapy and radiotherapy is only helpful for certain types of cancer, which can mean the success of chemoradiation can be different for each person. Depending on what type of cancer you have, you may undergo chemoradiation after your main treatment for cancer or after surgery to reduce your risk of remission.
Early-stage pancreatic cancer is one specific type of cancer that seems to benefit significantly from chemoradiation therapy. But, why does this combination work, and how much longer are survival rates with it? Let’s take a look.
About the Study
In the first trial used in the study, changing the type of chemotherapy given after surgery from a single drug to a multi-drug regimen greatly improved how long patients lived. Patients in the trial treated with the multi-drug regimen survived for an average of 4.5 years after treatment, substantially longer than expected.
The second trial examined whether giving chemoradiation before surgery, in addition to chemotherapy after, had any impact on survival. Results found that this combination of before and after care increased the number of patients who could successfully have their whole tumor removed. The team also found that people in this group also lived longer without their cancer coming back after surgery compared to those who received chemotherapy only after surgery.
To better understand how these treatments improve survival rates, let’s take a closer look at each one.
Altering Chemotherapy After Surgery (Adjuvant Therapy)
Since the 1990s, chemotherapy for pancreatic cancer involved a single-drug regimen with a drug known as gemcitabine (Gemzar). This drug has been the backbone for treating people with pancreatic cancer that can be removed with surgery. Typically, gemcitabine is given as ‘adjuvant chemotherapy,’ meaning it’s given after surgery.
Another chemotherapy regimen known as FOLFIRNOX, which consists of four different drugs, is the first choice for patients whose cancer has spread to other parts of the body (metastasized). FLFIRNOX is more effective than gemcitabine, however, doctors have long thought that it would have too many debilitating side effects. This is precisely what the researchers wanted to test.
Known as the PRODIGE 24 trial, scientists examined data from nearly 500 patients in Europe, all of whom were relatively healthy and under the age of 80. Participants were randomly assigned to receive 6 months of gemcitabine after surgery, or 6 months of a modified and somewhat less toxic version of FOLFIRINOX (mFOLFIRINOX).
The group found that while patients who received mFOLFIRINOX had more side effects than patients who received gemcitabine and were less likely to finish all of their chemotherapy, outcomes were better in the mFOLFIRINOX group. When compared to gemcitabine, mFOLRINOX nearly doubled the median length of time patients lived without remission, reported Thierry Conroy, M.D., of the Institut de Cancérologie de Lorraine in France, who led the trial. After 3 years, 63.5% of patients who had received mFOLFIRINOX were still alive, compared with 48.6% of patients who received gemcitabine.
“Such a long duration of survival for patients with this aggressive cancer type is something that I thought I would never see in my lifetime,” said Colin Weekes, M.D., Ph.D., of Massachusetts General Hospital, who was not involved in the study.
Advantages of Giving Chemoradiation Therapy Before Surgery (Neoadjuvant Therapy)
The next trial involved in the study examined whether utilizing chemoradiation therapy before surgery (known as neoadjuvant therapy), had better outcomes than chemotherapy alone afterward.
“Although adjuvant chemotherapy has been shown to extend survival of patients with early-stage pancreatic cancer, waiting until after surgery to give chemotherapy has potential problems,” explained Udo Rudloff, M.D., Ph.D., of NCI’s Center for Cancer Research, who was not involved in either trial. “When patients have surgery first, a proportion have complications and they aren’t healthy enough to receive chemotherapy, or there is a significant delay in starting chemotherapy,” he said.
In this trial, known as PREOPANC-1, researchers examined data from 246 patients, about half of which had tumors that were ‘borderline resectable.’ The participants were randomly assigned to one of two groups. One group would receive the standard treatment of gemcitabine after surgery only, and no chemoradiation before surgery. The other group also received gemcitabine after surgery but also underwent chemoradiation before.
PREOPANC-1 is still ongoing, so the results are preliminary. However, more than twice as many patients in the chemoradiation group than the chemotherapy alone group had their whole tumor removed successfully. Furthermore, patients who received chemoradiation lived for a median of 11.2 months without their disease progressing, compared with 7.9 months for patients in the standard chemotherapy group. After nearly two years, 42% of patients in the chemoradiation group were still alive, compared with only 30% in the standard chemotherapy group.
Implications of Chemoradiation Therapy for Pancreatic Cancer Patients
Improving the survival rates for pancreatic cancer patients is a major breakthrough. Together, these two clinical trials raise critical questions for the future of cancer treatment, Dr. Rudloff said. The first is whether mFOLFIRINOX should replace gemcitabine as neoadjuvant therapy, and the second is whether using newer types of radiation therapy, such as chemoradiation therapy, in neoadjuvant treatment regimens could further improve outcomes.
It’s important to note that these are early findings and that there are likely to be years before they become the standard practice for pancreatic cancer patients. However, while awaiting further trial results, more oncologists will likely turn to mFLORINOX both before and after treatment, says Allyson Ocean, M.D., a gastrointestinal oncologist at Weill Cornell Medicine and New York-Presbyterian, who was not involved in either trial.
More laboratory studies and clinical trials are needed to develop new treatments for pancreatic cancer, but these two clinical trials represent real, tangible progress.
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