K Klinghammer1, T Gauler2, A Dietz3, V Grünwald4, J Stöhlmacher5, S Knipping6, M Schroeder7, O Guntinas-Lichius8, N Frickhofen9, H-W Lindeman10, R Fietkau11, B Haxel12, C Große-Thie13, G Maschmeyer14, M Zipfel15, P Martus16, M Knoedler17, U Keilholz18. 1. Department of Hematology & Oncology, Charité University, Berlin, Germany. Electronic address: konrad.klinghammer@charite.de. 2. Department of Radiation Oncology, West German Cancer Center, University of Duisburg-Essen Medical School, Essen, Germany. 3. Department of Otolaryngology, Head and Neck Surgery, University Leipzig, Leipzig, Germany. 4. Interdisciplinary Urooncology, West German Cancer Center, Clinic for Internal Medicine (tumor research) and Clinic for Urology, University of Duisburg-Essen Medical School, Essen, Germany. 5. Department of Tumorgenetics Bonn, Bonn, Germany. 6. Department of Head and Neck Surgery, Klinikum Dessau, Dessau-Roßlau, Germany. 7. Department of Hematology and Oncology, Helios Duisburg, Duisburg, Germany. 8. Department of Otorhinolaryngology, Jena University Hospital, Jena, Germany. 9. Department of Hematology & Oncology and Palliative Care, HELIOS Dr Horst Schmidt Kliniken, Wiesbaden, Germany. 10. Department of Hematology & Oncology, KKH Hagen, Germany. 11. Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. 12. Department of Otolaryngology, AMEOS Klinikum Haldensleben, Haldensleben, Germany; Department of Otolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. 13. Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock, Germany. 14. Department of Hematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany. 15. Department of Internal Medicine III, University Hospital Bonn, Bonn, Germany. 16. Institute for Clinical Epidemiology and Applied Biometry, University of Tuebingen, Tuebingen, Germany. 17. University Cancer Center Leipzig, University Leipzig, Leipzig, Germany. 18. Charité Comprehensive Cancer Center, Berlin, Germany.
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.
RCT Entities:
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: Konrad Klinghammer; Luigi Lorini; Daan Nevens; Christian Simon; Jean-Pascal Machiels; Paolo Bossi Journal: Front Oncol Date: 2022-01-27 Impact factor: 6.244