As is done at Johns Hopkins, pancreatic cancer is best treated by a multidisciplinary team that includes primary care physicians, gastroenterologists, surgeons, pathologists, medical oncologists, and radiation oncologists. This team can best determine the combination of surgery, chemotherapy and radiation therapy that is best for a particular patient.
Chemotherapy and radiation therapy can be given to patients with advanced pancreatic cancer who are not candidates for surgery, and for patients who are candidates for surgery these therapies can be given before surgery (neoadjuvant therapy) or after surgery (adjuvant therapy). In these settings, chemotherapy can be given alone (chemotherapy) or in combination with radiation therapy (chemoradiation therapy).
Two drugs are commonly given when a patient receives chemotherapy. 5-fluorouracil (5FU) is a "thymidylate synthase inhibitor" and it functions by blocking the synthesis of the pyrimidine thymidine, a building block for DNA. The other drug is gemcitabine (also known under the brand name Gemzar). Gemcitabine is a "nucleoside analog," and it became the mainstay of chemotherapy after a randomized clinical trial comparing 5FU and gemcitabine which showed that gemcitabine was slightly superior in improving measures of quality of life such as pain and performance status. Gemcitabine is also associated with a slight improvement in overall survival.
More recently, combinations of chemotherapy are used to treat patients with advanced pancreatic cancer. For example, the combination of 5FU, leucovorin, oxaliplatin and irinotecan (FOLFIRINOX) was recently reported to be more effective than gemcitabine alone in a large series of patients with metastatic pancreatic cancer. It should be noted, however, that these combinations of chemotherapy are often associated with more side effects. For example, FOLFIRINOX treatment has a number of side effects, including low white blood cell count (neutropenia), low platelet counts (thrombocytopenia), diarrhea and sensory neuropathy.
Some patients, particularly those with borderline resectable pancreatic cancer, may be treated with chemotherapy or chemoradiation therapy before surgery. This serves two purposes. First, it may shrink the tumor slightly increasing the likelihood that the tumor can be completely removed surgically. Second, some patients given neoadjuvant therapy will be found to have metastatic cancer during the period of treatment. This metastatic cancer was presumably present at the start of neoadjuvant therapy, it just couldn't be detected. These patients will be deemed unresectable and spared the complications of surgery that is unlikely to have benefitted them.
Chemotherapy, or a combination of chemo therapy and radiation therapy, is usually given after surgery based on data from the Gastrointestinal Tumor Study Group (GTSG). A clinical trial performed by GTSG showed that 5FU plus radiation given after surgery improved survival over surgery alone. The adjuvant therapy used in these patients combines external beam radiotherapy to the tumor bed and adjacent tissues (> 45 Gy) delivered over the course of five to six weeks, with 5-fluorouracil-based chemotherapy given concurrently during the radiotherapy and for four months after the conclusion of the radiotherapy. Several clinical studies are now examining the effectiveness of FOLFIRINOX in the adjuvant setting.
In addition to the scenarios described above, radiation therapy in combination with chemotherapy is often given to patients with locally advanced but not metastatic pancreatic cancer. In this situation, radiation therapy can provide good local (in the area of the pancreas) control of the cancer, and it can alleviate a number of symptoms caused by the cancer such as pain.
There have been a number of advances in the way radiation therapy is delivered, including "intensity-modulated radiation therapy." These advances allow the radiation oncologist to deliver higher doses of radiation to the areas with cancer with less damage to the surrounding normal structures. In some instances the radiation can also be given over a shorter interval of time.
One thing that is clear is that we still have a long way to go in the treatment of pancreatic cancer. We cannot be satisfied with the status quo. For this reason, here at Johns Hopkins we strongly encourage patients with pancreatic cancer to consider participating in a clinical trial. Clinical trials allow researchers to test new drugs and new combinations of treatment. It is important to note that participating in a clinical trial does NOT mean the patient may be given a "placebo." In the vast majority of clinical trials two different treatments are compared. It is only through clinical trials that new and more effective treatments can be found.