Cancer cells divide and multiply rapidly within the mesothelioma lesions. These cancer cells carry special types of electrically charged elements that play a role during the cell division process. Other healthy cells in the upper torso multiply at a much slower rate, if at all, and thus rarely include the same electric properties as the dividing cancer cells.
TTFields Mechanism of Action
The NovoTTF-100L 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 the building blocks of these cells to pile up in such a way that the cells physically break apart. 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 fall apart 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 and clinical data also indicate that TTFields affect the healthy tissues within the upper torso much less than the cancer cells, probably since healthy cells within this anatomical region multiply at a much slower rate, if at all.
A summary of TTFields’ mechanism of action is illustrated in the following animation:
TTFIELDS ARE NOT APPROVED FOR THE TREATMENT OF MESOTHELIOMA. THE SAFETY AND EFFICACY OF TTFIELDS FOR MESOTHELIOMA HAS NOT BEEN ESTABLISHED.
Past preclinical experience
TTFields were found to have a profound inhibitory effect on the growth rate of mesothelioma cells grown in the lab. In a series of experiments, mesothelioma cells were shown to undergo cellular death under TTFields, while control mesothelioma cells grown under the same conditions, proliferated. Mesothelioma cells treated with TTFields in the lab had lost their ability to form colonies of cancer cells when seeded on special plates, while control, untreated mesothelioma cells preserved this ability. These results demonstrate the potential of TTFields to affect mesothelioma cells’ growth. Preclinical data do not always translate into similar effect in real patients. Therefore, the safety and 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 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-100L has previously been tested in a Pilot study for the treatment of non-small cell lung cancer the most common type of lung cancer, in combination with pemetrexed, a standard chemotherapy used for the treatment of this disease. TTFields were applied to the upper torso of patients in order to treat the disease in their lungs and upper abdomen. All patients included in this study had previously progressed following at least one other previous chemotherapy treatment.
The NovoTTF-100A System is approved by the FDA for the treatment of recurrent GBM and 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 System is not expected to have systemic side effects in patients suffering from malignant pleural mesothelioma. 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:
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 mesothelioma, it is not specific to this condition. The safety profile of the device for mesothelioma has not been established and may be different.