Characterization and management of dermatologic adverse events with the NovoTTF-100A System, a novel anti-mitotic electric field device for the treatment of recurrent glioblastoma.

The NovoTTF-100A System (NovoTTF™ Therapy, Novocure Inc.) is a device that delivers alternating electric fields (TTFields) to tumor cells and interferes with mitosis. It is approved for use as monotherapy for the treatment of recurrent glioblastoma (rGB). TTFields are delivered through insulated transducer arrays applied onto the shaved scalp and connected to a battery-operated field generator. The occurrence of dermatologic adverse events (dAEs) is primarily due to the continuous contact between the array-related components and the scalp for periods of 3-4 days (together with other risk factors). These dAEs may include allergic and irritant dermatitis, mechanical lesions, ulcers, and skin infection. The incidence of dAEs in the phase III trial (n = 116) was 16% (2% grade 2, 0% grade 3/4); the post-marketing surveillance program (n = 570) revealed 156 (21.8%) dAEs with some patients reporting more than one event. Prophylactic strategies for dAEs include proper shaving and cleansing of the scalp and array relocation. Treatment-based strategies are AE-specific and include topical or oral antibiotics, topical corticosteroids, and isolation of affected skin areas from adhesives and pressure. The addition of skin care strategies to the NovoTTF-100A System use will maximize adherence to therapy while maintaining quality of life, all of which contribute to the therapeutic benefit of NovoTTF Therapy in rGB.

[1]  A. Moritz,et al.  Studies of Thermal Injury: II. The Relative Importance of Time and Surface Temperature in the Causation of Cutaneous Burns. , 1947, The American journal of pathology.

[2]  H. Green,et al.  Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes , 1977, Nature.

[3]  D. Pounds,et al.  Transient cavitation in tissues during ultrasonically induced hyperthermia. , 1982, Medical physics.

[4]  William N. Rom,et al.  Environmental and occupational medicine , 1983 .

[5]  Occupational Skin Disease , 1985 .

[6]  M A Hardy,et al.  The biology of scar formation. , 1989, Physical therapy.

[7]  Photodamaged skin: a medical or a cosmetic concern? , 1990 .

[8]  Photodamaged skin: a medical or a cosmetic concern? , 1990, The Journal of international medical research.

[9]  S. Piantadosi,et al.  Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. , 1995, Lancet.

[10]  S. Piantadosi,et al.  Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas , 1995, The Lancet.

[11]  R. Anderson,et al.  Impact of patch testing on dermatology-specific quality of life in patients with allergic contact dermatitis. , 1997, American journal of contact dermatitis : official journal of the American Contact Dermatitis Society.

[12]  P. Steinert,et al.  Bricks and mortar of the epidermal barrier , 1999, Experimental & Molecular Medicine.

[13]  M J Gleason,et al.  Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  H. Maibach,et al.  Use tests: ROAT (repeated open application test)/PUT (provocative use test): an overview , 2000, Contact dermatitis.

[15]  C. Lyon,et al.  The spectrum of skin disorders in abdominal stoma patients , 2000, The British journal of dermatology.

[16]  R Paus,et al.  Controls of hair follicle cycling. , 2001, Physiological reviews.

[17]  A G Kibbi,et al.  Revised terminology in dermatology: a call for the new millennium. , 2001, Archives of dermatology.

[18]  K. Madison,et al.  Barrier function of the skin: "la raison d'être" of the epidermis. , 2003, The Journal of investigative dermatology.

[19]  E. Dekel,et al.  Disruption of cancer cell replication by alternating electric fields. , 2004, Cancer research.

[20]  The microanatomy of the epidermis in relation to trauma. , 2006, Journal of tissue viability.

[21]  R. Slavin,et al.  Allergic contact dermatitis. , 2006, The Medical clinics of North America.

[22]  E. Dekel,et al.  Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors , 2007, Proceedings of the National Academy of Sciences.

[23]  J. Brandner,et al.  The skin: an indispensable barrier , 2008, Experimental dermatology.

[24]  T. Fojo,et al.  Is there room for improvement in adverse event reporting in the era of targeted therapies? , 2008, Journal of the National Cancer Institute.

[25]  P. Wen,et al.  Role of a second chemotherapy in recurrent malignant glioma patients who progress on bevacizumab. , 2009, Neuro-oncology.

[26]  J. Vymazal,et al.  Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields) , 2009, BMC medical physics.

[27]  R. Mirimanoff,et al.  Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. , 2009, The Lancet. Oncology.

[28]  J. Nicolas,et al.  Allergic and irritant contact dermatitis. , 2009, European journal of dermatology : EJD.

[29]  L. Deangelis,et al.  Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma , 2009, Neurology.

[30]  Helen X. Chen,et al.  Adverse effects of anticancer agents that target the VEGF pathway , 2009, Nature Reviews Clinical Oncology.

[31]  A. Ehrlich,et al.  Stoma Dermatitis: Prevalent but Often Overlooked , 2010, Dermatitis : contact, atopic, occupational, drug.

[32]  V. Preedy,et al.  European Organization for Research and Treatment of Cancer , 2010 .

[33]  W. Kassouf,et al.  External stoma and peristomal complications following radical cystectomy and ileal conduit diversion: a systematic review. , 2010, Ostomy/wound management.

[34]  Uri Weinberg,et al.  Tumor treating fields: concept, evidence and future , 2011, Expert opinion on investigational drugs.

[35]  J. Segre,et al.  The skin microbiome , 2011, Nature Reviews Microbiology.

[36]  R. Weichselbaum,et al.  Improved survival time trends for glioblastoma using the SEER 17 population-based registries , 2012, Journal of Neuro-Oncology.

[37]  Santosh Kesari,et al.  Understanding glioblastoma tumor biology: the potential to improve current diagnosis and treatments. , 2011, Seminars in oncology.

[38]  J. Zenilman,et al.  New horizons for cutaneous microbiology: the role of biofilms in dermatological disease , 2011, The British journal of dermatology.

[39]  P. Gutin,et al.  NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. , 2012, European journal of cancer.

[40]  J. King,et al.  Adult glioblastoma multiforme survival in the temozolomide era: A population‐based analysis of Surveillance, Epidemiology, and End Results registries , 2012, Cancer.

[41]  K. Cowley,et al.  Insights into shaving and its impact on skin , 2012, The British journal of dermatology.

[42]  M. Lacouture,et al.  Grading dermatologic adverse events of cancer treatments: the Common Terminology Criteria for Adverse Events Version 4.0. , 2012, Journal of the American Academy of Dermatology.

[43]  M. Veldhoen,et al.  Epithelial barrier biology: good fences make good neighbours , 2012, Immunology.

[44]  Yoram Palti,et al.  Tumor treating fields: a new frontier in cancer therapy , 2013, Annals of the New York Academy of Sciences.

[45]  Moisture-associated skin damage: an overview for community nurses. , 2013, British journal of community nursing.

[46]  L. Deangelis,et al.  Glioblastoma and other malignant gliomas: a clinical review. , 2013, JAMA.

[47]  S. Kreth,et al.  Personalized treatment strategies in glioblastoma: MGMT promoter methylation status , 2013, OncoTargets and therapy.

[48]  Safety analysis of bevacizumab plus NovoTTF-100A in patients with recurrent malignant gliomas. , 2013 .

[49]  R. Wolf,et al.  Contact dermatitis: facts and controversies. , 2013, Clinics in dermatology.

[50]  M. Mrugala,et al.  Advances and challenges in the treatment of glioblastoma: a clinician's perspective. , 2013, Discovery medicine.