Nosova, M. V., Pokataev, I. A., Stativko, A. O., Stroyakovskiy, D. L., Zhukova, L. G., Lisitsyna, K. N., Sydykova, R. S., Kuzmina, E. S., Antonova, T. G., Lyadova, M. A., Sabitov, E. R., Parts, S. A., Kravtsov, S. A., Tsareva, E. V., Fedorova, A. N., Dolov, M. M., Feoktistova, P. S., & Galkin, V. N. (2025). Toxicity and Safety of Induction Chemotherapy in Locally Advanced Oropharynx, Hypopharynx and Larynx: Non-Randomized Study Comparing DCF and Immunochemotherapy (ICT) with PF-Pembrolizumab. Voprosy Onkologii, 70(6), 1096–1105. https://doi.org/10.37469/0507-3758-2024-70-6-1096-1105

Abstract

Introduction. DCF is a standard induction chemotherapy regimen for head and neck cancer. It provides a substantial objective response rate in patients (pts) with advanced head and neck cancer. However, the high toxicity of the regimen limits its applicability. A prospective, non-randomized study is evaluating the efficacy and safety of induction chemotherapy (ICT).

Aim. This work presents data comparing the safety of DCF and PF - pembrolizumab regimens and the risk of failure or non-completion of subsequent chemoradiotherapy (CRT).

Methods. The prospective, non-randomized phase II study enrolled PD-L positive patients (CPS>=1) with locally advanced stage III-IV squamous cell carcinoma of the oropharynx, larynx and pharynx. The patients received 3 cycles of ICT with pembrolizumab, cisplatin and 5-fluorouracil followed by CRT. The control group was assessed retrospectively and included patients who received DCF (docetaxel + cisplatin + 5-fluorouracil) followed by CRT during the same period.

Results. From April 2022 to July 2024, 120 pts were enrolled for ICT. The control group was collected retrospectively and included data from 115 pts. The incidence of grade 3-5 adverse events was 30 % and 30.4 % in the ICT and DCF groups, respectively (p = 1.00). During induction therapy, there were 6 deaths (5.2 %) in the DCF group, while there were no deaths in the PF - pembrolizumab group (p = 0.01). Due to the higher dose of cisplatin in the ICT group, a more significant trend towards a decrease in glomerular filtration rate (GFR) was observed compared to the DCF group, with a median decrease of 10.5 %. In all cases, the decrease in renal GFR did not result in the need for hemodialysis. 4 pts (4 %) in the ICT group and 12 pts (10 %, p = 0.06) in the DCF group could not receive radiation therapy due to general deterioration in health during induction therapy.

Conclusion. The induction regimen with PF-pembrolizumab has an acceptable toxicity profile. F The efficacy of ICT with PF-pembrolizumab requires further investigation. The study is registered on clinicaltrials.gov (No NCT05551767).

https://doi.org/10.37469/0507-3758-2024-70-6-1096-1105

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