Abstract
Purpose
Concurrent chemoradiotherapy (CRT) is the standard treatment for advanced head and neck squamous cell carcinoma. In this phase II randomized study, the efficacy and toxicity of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy (ICT) followed by concurrent CRT was compared with those after standard CRT alone in patients with locally advanced, unresectable head and neck cancer.
Patients and methods
Between January 2007 and June 2009, 66 patients with advanced (stage III or IV) unresectable squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, and larynx) were randomly assigned to two groups: one receiving two cycles of docetaxel, cisplatin, and 5-fluorouracil ICT followed by CRT with three cycles of cisplatin and one treated by CRT alone. Response rate, local tumor control (LTC), locoregional tumor control (LRTC), overall survival (OS), progression-free survival (PFS), and toxicity results were assessed.
Results
Three patients from the ICT + CRT group did not appear at the first treatment, so a total of 63 patients were evaluated in the study (30 ICT + CRT group and 33 CRT group). Three patients died of febrile neutropenia after ICT. The median follow-up time for surviving patients was 63 months (range 53–82 months). The rate of radiologic complete response was 63 % following ICT + CRT, whereas 70 % after CRT alone. There were no significant differences in the 3-year rates of LTC (56 vs. 57 %), LRTC (42 vs. 50 %), OS (43 vs. 55 %), and PFS (41 vs. 50 %) in the ICT + CRT group and in the CRT group, respectively. The rate of grade 3–4 neutropenia was significantly higher in the ICT + CRT group than in the CRT group (37 and 12 %; p = 0.024). Late toxicity (grade 2 or 3 xerostomia) developed in 59 and 42 % in the ICT + CRT and CRT groups, respectively.
Conclusion
The addition of ICT to CRT did not show any advantage in our phase II trial, while the incidence of adverse events increased. The three deaths as a consequence of ICT call attention to the importance of adequate patient selection if ICT is considered.
Zusammenfassung
Hintergrund
Simultane Chemoradiotherapie (CRT) ist eine Standardtherapie beim fortgeschrittenen Plattenepithelkarzinom im Kopf-Hals-Bereich. In dieser randomisierten Phase-II-Studie wurden die Wirksamkeit und Toxizität einer Induktionschemotherapie (ICT) mit Docetaxel, Cisplatin und 5-Fluorouracil gefolgt von simultaner CRT mit der CRT allein bei Patienten mit lokal fortgeschrittenen, irresektablen Kopf-Hals-Tumoren verglichen.
Patienten und Methoden
Zwischen Januar 2007 und Juni 2009 wurden 66 Patienten mit fortgeschrittenem (Stadium III oder IV), inoperablem Plattenepithelkarzinom im Kopf-Hals-Bereich (Mundhöhle, Oropharynx, Hypopharynx, Larynx) nach dem Zufallsprinzip in 2 Gruppen eingeteilt. Die eine Gruppe erhielt 2 Zyklen der Docetaxel-, Cisplatin- und 5-Fluorouracil-ICT gefolgt von CRT mit 3 Zyklen Cisplatin, die andere Gruppe erhielt nur CRT. Ansprechrate, lokale Tumorkontrolle (LTC), lokoregionale Tumorkontrolle (LRTC), Gesamtüberleben (OS), progressionsfreies Überleben (PFS) und toxischer Effekt wurden verglichen.
Ergebnisse
Drei Patienten der Gruppe mit ICT + CRT erschienen bei der ersten Behandlung nicht, so dass insgesamt 63 Patienten in der Studie ausgewertet wurden (30 in der Gruppe ICT + CRT, 33 in der CRT-Gruppe). Drei Patienten starben an febriler Neutropenie nach ICT. Die mediane Nachbeobachtungszeit der überlebenden Patienten betrug 63 Monate (Spanne 53–82 Monate). Die Rate des radiologischen vollständigen Ansprechens war 63 % nach ICT + CRT vs. 70 % nach CRT allein. Es gab keinen signifikanten Unterschied in der 3-Jahres-Rate bei LTC (56 vs. 57 %), LRTC (42 vs. 50 %), OS (43 vs. 55 %) und PFS (41 vs. 50 %) zwischen der Gruppe mit ICT + CRT und den mit CRT behandelten Patienten. Die Rate von Neutropenie mit einem Grad 3–4 lag in der Gruppe mit ICT + CRT deutlich höher als in der CRT-Gruppe (37 und 12 %; p = 0,024). Späte Toxizität (Grad-2- und Grad-3-Xerostomie) ereignete sich in der Gruppe mit ICT + CRT und in der CRT-Gruppe in jeweils 59 vs. 42 %.
Schlussfolgerung
Die Kombination von ICT und CRT erbrachte in unserer Phase-II-Studie keine Vorteile, wobei die Gesamtinzidenz der unerwünschten Ereignisse stieg. Die 3 Todesfälle infolge ICT weisen auf die Wichtigkeit der Patientenauswahl im Falle einer ICT-Behandlung hin.
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Z. Takácsi-Nagy, E. Hitre, É. Remenár, F. Oberna, C. Polgár, T. Major, M. Gödény, J. Fodor, and M. Kásler state that there are no conflict of interest.
All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and 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.
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Takácsi-Nagy, Z., Hitre, E., Remenár, É. et al. Docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by chemoradiotherapy or chemoradiotherapy alone in stage III–IV unresectable head and neck cancer. Strahlenther Onkol 191, 635–641 (2015). https://doi.org/10.1007/s00066-015-0829-z
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DOI: https://doi.org/10.1007/s00066-015-0829-z