Cetuximab, fluorouracil and cisplatin with or without docetaxel for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CeFCiD): an open-label phase II randomised trial (AIO/IAG-KHT trial 1108)

Klinghammer K, Gauler T, Dietz A, Grünwald V, Stöhlmacher J, Knipping S, Schroeder M, Guntinas-Lichius O, Frickhofen N, Lindeman HW, Fietkau R, Haxel B, Große-Thie C, Maschmeyer G, Zipfel M, Martus P, Knoedler M, Keilholz U (2019)

Publication Type: Journal article

Publication year: 2019

Journal

European Journal of Cancer Elsevier

Book Volume: 122

Pages Range: 53-60

DOI: 10.1016/j.ejca.2019.08.018

Abstract

Background: The combination of cisplatin, 5-fluorouracil (5-FU) and cetuximab (PFC) is the reference first-line treatment for recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). We analysed whether treatment intensification by the addition of docetaxel to PFC improved efficacy in R/M SCCHN. Methods: A total of 180 patients with R/M SCCHN (1:1) were assigned to receive either cisplatin (40 mg/m2), docetaxel (40 mg/m2) and 5-FU (2000 mg/m2) at days 1 and 8 and cetuximab (400/250 mg/m2) at days 1, 8 and 15 (DPFC) or standard cisplatin (100 mg/m2) at day 1, 5-FU (1000 mg/m2) at days 1–4 and cetuximab (400/250 mg/m2) at days 1, 8 and 15 (PFC). Chemotherapy was repeated every 21 days and continued for a maximum of 6 cycles in absence of disease progression or limiting toxicity, followed by cetuximab maintenance (500 mg/m2 every 2 weeks). The primary end-point was progression-free survival (PFS). Results: A preplanned interim analysis for toxicity after 20 patients/arm revealed excessive grade 3 and 4 gastrointestinal (65%) and infectious toxicities (35%) in arm A, which led to dose reduction of cisplatin to 30 mg/m2 and 5-FU to 1000 mg/m2 for subsequent patients. With a median follow-up of 2 years, grade 4 toxicities were 21.3% vs. 30.8% for DPFC and PFC, respectively. More treatment-related deaths occurred with DPFC vs. PFC, with 11.2% and 6.6%, respectively. For DPFC and PFC, the median PFS was 6.3 vs. 6.4 months (hazard ratio [HR] = 0.97, p = 0.87), the median overall survival was 8.9 vs. 10.6 months (HR = 1.29 p = 0.1) and response rates were 38.2% vs. 31.9% (p = 0.9), respectively. Conclusions: DPFC failed to improve efficacy in R/M SCCHN. On the contrary, a high toxicity and mortality rate was detected in both arms, which underscores the vulnerability of patients with R/M SCCHN, and research on the need for further optimisation of the front-line chemotherapy backbone is ongoing.

Authors with CRIS profile

Rainer Fietkau Lehrstuhl für Strahlentherapie

Involved external institutions

Charité - Universitätsmedizin Berlin DE Germany (DE) Universität Duisburg-Essen (UDE) DE Germany (DE) Universität Leipzig DE Germany (DE) Städtisches Klinikum Dessau DE Germany (DE) Universitätsklinikum Jena DE Germany (DE) Horst-Schmidt-Kliniken DE Germany (DE) AMEOS Klinikum Haldensleben GmbH DE Germany (DE) Universitätsmedizin Rostock DE Germany (DE) Klinikum Ernst von Bergmann DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE)

How to cite

APA:

Klinghammer, K., Gauler, T., Dietz, A., Grünwald, V., Stöhlmacher, J., Knipping, S.,... Keilholz, U. (2019). Cetuximab, fluorouracil and cisplatin with or without docetaxel for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CeFCiD): an open-label phase II randomised trial (AIO/IAG-KHT trial 1108). European Journal of Cancer, 122, 53-60. https://doi.org/10.1016/j.ejca.2019.08.018

MLA:

Klinghammer, K., et al. "Cetuximab, fluorouracil and cisplatin with or without docetaxel for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CeFCiD): an open-label phase II randomised trial (AIO/IAG-KHT trial 1108)." European Journal of Cancer 122 (2019): 53-60.

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