Cancer cells divide and multiply rapidly within the pancreatic cancer tumor. These cancer cells carry special types of electrically charged elements that play a role during the cell division process. Other healthy cells in the abdominal region multiply at a much slower rate, if at all, and/or have other different properties such as a different size, compared to the cancer cells. Thus, normal cells rarely include the same electric properties as the dividing cancer cells and are not expected to be affected by TTFields.

TTFields Mechanism of Action

The NovoTTF-100L(P) device used in this trial delivers very low intensity, alternating electric fields to the tumor site through the skin and other superficial tissues. These fields are known as Tumor Treating Fields or TTFields. Due to the unique shape of cancer cells when they are multiplying, TTFields have been shown to cause certain building blocks of these cells to pile up in such a way that destroys the entire dividing cell. In addition, cancer cells also contain miniature building blocks that move essential parts of the cells from place to place during division. TTFields have been shown to cause these building blocks to fail to function normally since they have a special type of electric charge. As a result of these two effects, preliminary study data indicate that cancer tumor growth is inhibited after continuous exposure to TTFields. Preclinical data also indicate that TTFields affect the healthy tissues within the abdominal region much less than the cancer cells, if at all.

A summary of TTFields’ mechanism of action is illustrated in the following animation:

TTFIELDS ARE NOT APPROVED FOR THE TREATMENT OF PANCREATIC CANCER. THE SAFETY AND EFFECTIVENESS OF TTFIELDS FOR PANCREATIC CANCER HAS NOT BEEN ESTABLISHED.

Past preclinical experience

TTFields were found to have an inhibitory effect on the growth rate of pancreatic cancer cells grown in the lab. In a series of experiments, dividing pancreatic cancer cells were shown to have severe structural abnormalities under TTFields, leading to their death, while control pancreatic cells grown under the same conditions proliferated. Pancreatic cancer cells treated with TTFields in combination with standard chemotherapy used for the treatment of patients suffering from this condition, have demonstrated an even greater anti-tumor effect. These are some of the preclinical results demonstrating the potential of TTFields to affect pancreatic cancer cells’ growth. Preclinical data do not always translate into similar effect in real patients. Therefore, the safety and preliminary efficacy of TTFields must be verified in clinical trials.

Past clinical experience

A number of systems developed to deliver TTFields to different tumors have been tested to date. The main difference between the previously tested systems and the NovoTTF-100L(P) is the frequency of TTFields provided by each system. The frequency is adjusted by the manufacturer of the systems in order to optimize the treatment for each treated cancer, based on data from laboratory experiments.

The NovoTTF-100A System is approved by the FDA for the treatment of newly diagnosed and recurrent GBM. The same system has a CE Mark in Europe for the treatment of GBM, while the NovoTTF-100L has a CE Mark in Europe for the treatment of non-small-cell lung cancer.

Side effects

Based on the science behind TTFields and the clinical results to date, the NovoTTF-100L(P) System is not expected to have systemic side effects in patients suffering from pancreatic adenocarcinoma. In previous studies performed with the NovoTTF-100 Systems, many patients have experienced local skin irritation beneath the transducer arrays.
In a previous clinical trial for non-small-cell lung cancer, the following adverse events were reported:

Allergic reaction to the adhesive or to the gel (26.8% of patients)
Open sores ulceration or blisters underneath the transducer arrays (9.7%)
Local heat and tingling “electric” sensation beneath the transducer array (2.4%)
Fatigue (24.3%)

The information provided in this website is partial, and you should consult with your treating physician concerning the complete safety profile of TTFields.

Please note that while the adverse event information from previous clinical trials may be relevant for the use of the device for pancreatic cancer, it is not specific to this condition. The safety profile of TTFields in pancreatic cancer has not been established and may be different.