1. Susman, Ed

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SAN FRANCISCO-Treatment with a combination of chemotherapy and electric stimulation using Tumor Treating Fields (TTFields) technology appeared to offer patients diagnosed with advanced pancreatic adenocarcinoma an alternative to just chemotherapy (Abstract e15269).

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The 20 patients in the pilot study achieved a mean 14.9 month overall survival, with 55 percent of the patients achieving at least 1 year survival, said Uri Weinberg, MD, PhD, Vice President for Research and Development at Novocure, Inc., based in Haifa, Israel, at his poster presentation during the 2016 Gastrointestinal Cancers Symposium.


He told Oncology Times the median progression free survival was 8.3 months, and 56 percent of the patients achieved a 6-month progression free survival. Of patients with evaluable tumors, 30 percent achieved an objective partial response, and another 30 percent of patients achieved disease stabilization.


"I believe this would be considered a fairly good outcomes considering that these patients had locally advanced pancreatic cancer or metastatic disease," he said. "But," he cautioned, "this is early stages of use of this technology and this is a single-arm study. We are definitely planning to continue to develop this treatment in a randomized trial."


Weinberg said the trial would recruit another 20 patients who will receive gemcitabine, nab-paclitaxel, and TTFields treatment.


"TTFields are alternating electric fields delivered to the region of the tumor by means of noninvasive transducer arrays surrounding the abdominal region," Weinberg explained.


"TTFields have shown an antimitotic effect by interfering with mitotic spindle formation. The anti-proliferative effect of TTFields on pancreatic cancer has been demonstrated in a series of in vitro and in vivo experiments. TTFields use low-intensity alternating electric fields. We are able to interfere with cell activity by acting on the charged molecules within the cell."


Amit Mahipal, MBBS, MPH, Senior Associate Consultant in Medical Oncology at the Mayo Clinic and Assistant Professor of Oncology at the Mayo Medical School, Rochester, Minn., noted, "This is a bit of a novel approach, although I think in the past three or four years it has been tested in other tumor types. I, myself, have not used it as yet.


"Transponders are put on the skin and the electric current is induced. In this trial, the treatment was paired with concurrent chemotherapy," Mahipal noted. "In other cancer treatments, TTFields has been used as a single-agent therapy. Other studies have shown that, if you use it with chemotherapy, then the chemotherapy can be potentiated."


TTFields Tolerable, Safe

In conducting the PANOVA study, the researchers enrolled patients who had not received previous chemotherapy or radiation for their histologically-confirmed pancreatic adenocarcinoma. Patients were treated with gemcitabine 1,000 mg/m2 once weekly for up to seven weeks, with subsequent infusions on days 1, 8, 15, and then repeating the cycle every 28 days. Continuous TTFields (150kHz) for at least 18 hours a day was delivered until radiologically-proven progression or unacceptable toxicity.


The patients in the study were a median age of 73 years, although they ranged from 49 years to 81 years. Half of the patients had smoking histories. Twelve of the patients in the study were women. Most patients had good performance status-80 percent having an ECOG score of 1. Twelve of the patients were diagnosed with distant metastases; the other eight patients were diagnosed with locally advance pancreatic adenocarcinoma.


Weinberg and colleagues reported the median compliance with TTFields was 78 percent-or 14 hours a day. The median duration of use of TTFields in this study was five months. Ten of the patients or 50 percent of the participants reported some degree of treatment-related skin toxicity, but just two of those patients had grade 3 skin toxicity and in both cases the skin involvement resolved with appropriate treatment. The researchers said there were no serious adverse events related to treatment with TTFields.


"TTFields concomitant to gemcitabine are tolerable and safe for advanced pancreatic cancer patients," the researchers suggested.


"We do not have plans to use this techniques at the Mayo Clinic, to my knowledge at least," Mahipal said. "But use of TTFields looks intriguing and it is something to watch out for in the future. I think it requires a bit of knowledge and expertise in learning how to apply these electrodes. If this treatment does get approved for treatment of pancreatic cancer, I think it is something that will be used mainly in academic centers before it moves out into the community.


Mahipal said the treatment has plausible biologic mechanisms of action. The electric current, he said, would stimulate cells and make them more vulnerable to chemotherapy.


Ed Susman is a contributing writer.