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Prospective phase II trial of cetuximab plus VMAT-SIB in locally advanced head and neck squamous cell carcinoma

Feasibility and tolerability in elderly and chemotherapy-ineligible patients

Prospektive Phase-II-Studie mit Cetuximab in Kombination mit VMAT-SIB bei lokal fortgeschrittenem Kopf-Hals-Plattenepithelkarzinom

Realisierbarkeit und Tolerabilität bei älteren und nicht für Chemotherapie geeigneten Patienten

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Abstract

Introduction

Cetuximab plus radiotherapy (RT) may be an effective alternative to chemoradiation in locally advanced head and neck squamous cell carcinoma (LASCCHN) patients. We analyzed a group of patients treated at our institute with cetuximab plus volumetric modulation arc therapy (VMAT) with the RapidArc technique in a simultaneous integrated boost (SIB) regime. The primary end point was the assessment of acute toxicity and the feasibility of the combined approach.

Materials and methods

Between December 2008 and March 2010, 22 patients were submitted to IMRT-SIB plus cetuximab for radical intent in case of LASCCHN. None of the patients was suitable for chemotherapy because of important comorbidities (the majority suffered of heart chronic diseases). All patients underwent planning CT (additional image modalities were acquired for contouring purposes in the same treatment position: MRI in 12 and FDG-PET in 4 out of 22 patients). VMAT, by means of RapidArc, and SIB with two dose levels of 54.45 Gy and 69.96 Gy in 33 fractions were adopted. All patients included in the analysis were concomitantly treated with cetuximab: administration of the drug was initiated 1 week before RT at a loading dose of 400 mg/m2 body surface area over a period of 120 min, follow by a weekly 60 min infusion of 250 mg/m2 for the duration of RT. Patients were assessed for toxicities according to the Radiation Therapy Oncology Group (RTOG) criteria.

Results

All but 2 patients completed treatment and achieved the minimum follow-up of 12 months after the end of the treatment. Of the 22 patients, 18% (4 patients) showed grade 1, 36% (8 patients) grade 2, and 36% (8 patients) showed grade 3 dermatitis, while 9% (2 patients) had grade 1, 36% (8 patients) grade 2, and 45% (10 patients) had grade 3 mucositis/stomatitis. No grade 4 toxicities were recorded. Considering blood parameters, 3 cases of grade 1 anemia and 1 case of grade 2 thrombocytopenia were observed. Nobody required feeding tube placement during treatment.

Conclusion

The here reported toxicity data are promising and encouraging in regard to the adoption of moderate hypofractionation with VMAT-SIB techniques, when cetuximab is concomitantly administered.

Zusammenfassung

Einführung

Cetuximab und Radiotherapie (RT) kann für Patienten mit lokal fortgeschrittenen Kopf-Hals-Plattenepithelkarzinomen (LASCCHN) eine effektive Alternative zur Radiochemotherapie darstellen. Wir haben eine Gruppe von Patienten analysiert, die in unserer Klinik mit Cetuximab und RapidArc®, einer volumetrisch modulierten Arc-Therapie (VMAT), behandelt wurden. Dabei haben wir das simultan integrierte Boost- (SIB-)Verfahren verwendet. Primärer Endpunkt waren die Akutoxizität und die Realisierbarkeit dieses kombinierten Vorgehens.

Patienten und Methoden

Zwischen Dezember 2008 und März 2010 wurden 22 LASCCHN-Patienten der IMRT-SIB- und Cetuximab-Behandlung in kurativer Absicht zugeführt. Aufgrund relevanter Komorbidität (die Mehrheit litt an chronischen Herzerkrankungen) war keiner dieser Patienten für eine Chemotherapie geeignet. Für alle Patienten wurde ein Planungs-CT erstellt; in derselben Behandlungsposition wurden bei 12 von 22 Patienten zusätzlich ein MRT und bei 4 von 22 Patienten ein FDG-PET erstellt. Eine VMAT-Behandlung, in diesem Fall RapidArc mit SIB in 2 Dosierungen (54,45 Gy und 69,96 Gy in 33 Fraktionen), wurde durchgeführt. Gleichzeitig wurden alle Patienten in dieser Studie mit Cetuximab behandelt. Die Verabreichung des Medikaments begann eine Woche vor der Strahlentherapie; dabei wurde eine Dosis von 400 mg/m2 über 120 min gegeben. Danach wurde über die gesamte Dauer der Strahlentherapie wöchentlich 250 mg/m2 über 60 min als Infusion verabreicht. Die Toxizität wurde anhand der Kriterien der „Radiation Therapy Oncology Group“ (RTOG) beurteilt.

Ergebnisse

Mit Ausnahme von 2 Patienten beendeten alle Patienten die Behandlung und erreichten nach Abschluss der Therapie ein Follow-up von mindestens 12 Monaten. 18% (4/22) der Patienten zeigten eine G1-, 36% (8/22) eine G2- und 36% (8/22) eine G3-Dermatitis. Bei 9% (2/22) der Patienten entwickelte sich eine G1-, bei 36% (8/22) eine G2- und bei 45% (10/22) eine G3-Mukositis/Stomatitis. Es wurden keine G4-Toxizitäten festgestellt. Bei den Blutwerten wiesen 3 Patienten eine G1-Anämie und ein Patient eine G2-Thrombozytopenie auf. Kein Patient benötigte während der Behandlung eine künstliche Ernährung.

Zusammenfassung

Die hier gezeigten Toxizitätsdaten sind vielversprechend und ermutigend hinsichtlich des Einsatzes einer hypofraktionierten VMAT-SIB-Behandlungstechnik bei gleichzeitiger Gabe von Cetuximab.

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The corresponding author states that there are no conflicts of interest.

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Authors and Affiliations

  1. Radiotherapy and Radiosurgery, Humanitas Cancer Center, Istituto Clinico Humanitas, Via Manzoni 56, 20098, Rozzano (Milan), Italy

    F. Alongi Dr., M. Bignardi, S. Pentimalli, P. Mancosu, G. Reggiori, O. Spahiu & M. Scorsetti

  2. Oncology, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano (Milan), Italy

    I. Garassino, R. Cavina & A. Santoro

  3. Head and Neck Surgery, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano (Milan), Italy

    A. Poletti

  4. Medical Oncology, Ospedale San Paolo, Milan, Italy

    D. Ferrari & P. Foa

  5. Head and Neck Surgery, Ospedale S.Giuseppe, Milan, Italy

    A. Bigoni, A. Dragonetti & P. Salvatori

  6. Medical Physics Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland

    A. Fogliata & L. Cozzi

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  1. F. Alongi Dr.
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  2. M. Bignardi
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Correspondence to F. Alongi Dr..

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Alongi, F., Bignardi, M., Garassino, I. et al. Prospective phase II trial of cetuximab plus VMAT-SIB in locally advanced head and neck squamous cell carcinoma. Strahlenther Onkol 188, 49–55 (2012). https://doi.org/10.1007/s00066-011-0006-y

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