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Hedgehog pathway inhibitor in combination with radiation therapy for basal cell carcinomas of the head and neck

First clinical experience with vismodegib for locally advanced disease

Inhibitor der Hedgehog-Signalkaskade in Kombination mit Bestrahlung beim Basalzellkarzinom der Kopf-Hals-Region

Erste klinische Erfahrungen mit Vismodegib bei lokal fortgeschrittener Erkrankung

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Abstract

Background

Definitive radiotherapy and vismodegib, an oral inhibitor of the hedgehog pathway, are both established treatment options for locally advanced basal cell carcinomas (BCC). Both have shown good results in local tumor control; however, the effects concerning advanced tumors are often not of a lasting nature and to date no systematic data about the combination of the two modalities are available.

Patients and methods

We retrospectively analyzed four patients who received vismodegib and radiotherapy in combination. Radiation doses varied between 50.4 Gy and 66.0 Gy. Three patients had recurrent BCC. One patient had locoregional lymph node involvement. Vismodegib was taken once a day (150 mg) during the entire time of irradiation and beyond upon instructions of the attending dermatologist.

Results

In three cases a persistent complete response was observed, in one case the tumor remained stable for approximately 6 months until further tumor progression was documented. The combined therapy was well tolerated in all cases. No exceptional side effects pointing at a drug–radiation interaction were observed.

Conclusion

The combination of vismodegib and radiation seems feasible and the initial results are promising. In our cohort, there was no increase in unexpected side effects. Further research is needed to evaluate the significance of this combined therapy.

Zusammenfassung

Hintergrund

Sowohl definitive Radiotherapie als auch Vismodegib, ein oraler Inhibitor der Hedgehog-Signalkaskade, sind etablierte Behandlungsoptionen für lokal fortgeschrittene Basalzellkarzinome (BCC). Beide Therapien zeigen für sich gute Ansprechraten, aber die lokale Tumorkontrolle ist oft nicht dauerhaft und bis heute existieren kaum Daten über eine Kombination der beiden Modalitäten.

Patienten und Methoden

Wir analysierten retrospektiv vier Patientenfälle nach simultaner Applikation von Vismodegib und Bestrahlung. Die Bestrahlungsdosis variierte zwischen 50,4 Gy und 66,0 Gy. Drei der Patienten hatten ein rezidiviertes BCC. Ein Patient hatte einen befallenen regionalen Lymphknoten. Vismodegib wurde einmal täglich (150 mg) über die gesamte Radiotherapie und nach deren Beendigung, je nach Empfehlung des betreuenden Dermatologen, eingenommen.

Ergebnisse

In drei Fällen konnte ein länger andauerndes Ansprechen beobachtet werden. In einem Fall verblieb der Tumor für 6 Monate stabil, bevor eine erneute Tumorprogression festgestellt werden konnte. Die kombinierte Therapie wurde in allen Fällen gut vertragen. Es konnten keine unerwarteten Nebenwirkungen beobachtet werden, die auf eine supraadditive Toxizität deuten könnten.

Schlussfolgerung

Die Kombination von Vismodegib und Radiotherapie erscheint möglich. Die ersten Ergebnisse sind vielversprechend. In unserer Kohorte konnte keine erhöhte Toxizität beobachtet werden. Künftige Studien sollten den Stellenwert dieser kombinierten Therapie untersuchen.

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Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany

    Björn Schulze MD, Claus Rödel MD & Panagiotis Balermpas MD

  2. Department of Dermatology, University Hospital Johann Wolfgang Goethe University, Frankfurt, Germany

    Markus Meissner MD

  3. Department of Craniofacial and Plastic Surgery, University Hospital Johann Wolfgang Goethe University, Frankfurt, Germany

    Shahram Ghanaati DMD, MD

  4. Department of Diagnostic and Interventional Radiology, University Hospital Johann Wolfgang Goethe University, Frankfurt, Germany

    Iris Burck MD

Authors
  1. Björn Schulze MD
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  2. Markus Meissner MD
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  3. Shahram Ghanaati DMD, MD
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  4. Iris Burck MD
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  5. Claus Rödel MD
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  6. Panagiotis Balermpas MD
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Corresponding author

Correspondence to Panagiotis Balermpas MD.

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Conflict of interest

B. Schulze, M. Meissner, S. Ghanaati, I. Burck, C. Rödel, and P. Balermpas state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies. Consent was obtained from all patients identifiable from images or other information within the manuscript. No underage patients were included.

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Schulze, B., Meissner, M., Ghanaati, S. et al. Hedgehog pathway inhibitor in combination with radiation therapy for basal cell carcinomas of the head and neck. Strahlenther Onkol 192, 25–31 (2016). https://doi.org/10.1007/s00066-015-0902-7

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  • DOI: https://doi.org/10.1007/s00066-015-0902-7

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