A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer

Lung Cancer. 2013 Sep;81(3):445-450. doi: 10.1016/j.lungcan.2013.06.025. Epub 2013 Jul 23.


Background: Low intensity, intermediate frequency, alternating electric fields (Tumor Treating Fields; TTFields) exhibit anti-mitotic activity in cancer cells. Promising preclinical data have led to a single arm phase I/II trial in NSCLC patients.

Methods: Forty-two inoperable stage IIIB (with pleural effusion) and IV NSCLC patients who had had tumor progression received pemetrexed 500 mg/m(2) iv q3w together with daily TTFields therapy until disease progression. The primary endpoint was time to "in-field" progression.

Results: Median age for all patients was 63 years, 76% had stage IV disease, 78% had adenocarcinoma and 17% had performance status of 2. The median time to in-field progression was 28 weeks and the median time to systemic progression was 22 weeks. Six patients (14.6%) had a partial remission (PR) and 20 had stable disease (SD) (48.8%). Median overall survival was 13.8 months and 1 year survival rate was 57%. There were no TTFields-related serious adverse events.

Conclusions: The combination of TTFields and pemetrexed as a second line therapy for NSCLC is safe and potentially more effective than pemetrexed alone. TTFields improved disease control within the treatment field and a phase III study is planned to further investigate its role as a novel treatment in NSCLC.

Keywords: In-field progression; Local control; Low intensity electric fields; Metastatic NSCLC; NovoTTF; Second line treatment.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Combined Modality Therapy
  • Female
  • Glutamates / administration & dosage
  • Glutamates / adverse effects
  • Glutamates / therapeutic use*
  • Guanine / administration & dosage
  • Guanine / adverse effects
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Humans
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Pemetrexed
  • Physical Therapy Modalities* / adverse effects
  • Treatment Outcome


  • Antineoplastic Agents
  • Glutamates
  • Pemetrexed
  • Guanine