Is the Substitution of Cisplatin and 5-Flurouracil with Carboplatin and Capecitabine in the Treatment of Locally Advanced Head Neck Cancers (HNC) an Option? A Retrospective Single Center Analysis
Authors: Mireștean Camil Ciprian , Iancu Roxana Irina , Iancu Dragoș Petru Teodor , Stan Mihai Cosmin , Bădulescu Florinel 
Published: February 2025

Abstract
Cytotoxic chemotherapy and radiotherapy, in sequential and concurrent combination, represent the basis of multimodal treatment in locally advanced head and neck cancers (HNC). In the relapsed and metastatic stage of disease, chemotherapy was the main therapeutic method, and currently it is included in therapeutic regimens in association with immune checkpoint inhibitors (ICI) and molecular targeted therapies. Cisplatin is considered the most active agent in HNC, but its substitution with Carboplatin and 5-Fluorouracil with the oral analogue Capecitabine is accepted in certain cases. The aim of the study which included 190 cases of locally advanced recurrent and metastatic HNC treated multimodally in the Oncology Clinic of the Craiova Emergency County Hospital was the retrospective evaluation of the therapeutic benefit of Carboplatin and Capecitabine in different chemotherapy/chemo-radiotherapy protocols. The number of chemotherapy courses, the maximum number of agents included in the therapeutic regimens, and the involvement of the total dose of radiotherapy in the prognosis were also evaluated. The results confirm an initial and long-term benefit of Cisplatin, but medium-term OS is superior in groups treated with chemotherapy regimens that include Carboplatin. The use of Capecitabine as a single agent or in poly-chemotherapy regimens was beneficial in the first two years of follow-up, with superior OS for regimens that associate other chemotherapy agents including 5-Fluorouracil (5FU). The benefit in OS was also demonstrated in the case of increasing the number of agents per course, from 1 to 2 and 3, instead the association of 4 chemotherapeutic agents led to unfavorable results. The superiority of OS for irradiation doses over 60 Gy versus the dose of 50 Gy becomes significant especially after the first 3 years post-treatment. The heterogeneity of the inclusion criteria, the retrospective nature of the study, but also the evolution of the treatments during the evaluation period of the study data (20 years) could be considered the limits of this analysis. The study highlights for the first time a benefit on an average post-therapeutic time interval of Carboplatin in favor of Cisplatin. However, the short- and long-term results confirm the literature superiority data for Cisplatin. The small number of cases in the group treated with Capecitabine justifies the need for new trials, but also the inclusion of a larger number of patients in retrospective studies with long follow-up periods and more uniform inclusion criteria. Total radiation dose > 60 Gy is also a prognostic factor. The results demonstrate that the agents Carboplatin and Capecitabine could be considered as substitutes, but only in cases ineligible for the standard regimens or in situations of unavailability of the agents Cisplatin and 5-Fluorouracil.