Comparison of Carboplatin With 5-Fluorouracil vs. Cisplatin as Concomitant Chemoradiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma.

Saskia H Hanemaaijer,Johannes A Langendijk,Jourik A Gietema,Jan Buter,Sjoukje F Oosting,Bert Van Der Vegt,Iris C Kok,C René Leemans,Marije R Vergeer,Jens Voortman,Marcel A T M Van Vugt,Boudewijn E C Plaat,Rudolf S N Fehrmann

doi:10.3389/fonc.2020.00761

Abstract

Background: Chemoradiotherapy (CRT) including three cycles of cisplatin is considered the standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, around one-third of the patients cannot complete cisplatin because of toxicity. Carboplatin plus 5-fluorouracil (carbo-5FU) is another accepted treatment option with a different toxicity profile. We compared tolerability and efficacy of concomitant carbo-5FU and cisplatin.Patients and Methods: We conducted a retrospective analysis of LA-HNSCC patients treated with CRT in two Dutch cancer centers between 2007 and 2016. All patients received intensity-modulated radiotherapy. One center routinely administered carboplatin 300–350 mg/m2 at day 1, 22, and 43 followed by 5FU 600 mg/m2/day for 96 h. The other center used cisplatin 100 mg/m2 at day 1, 22, and 43. The primary endpoint of this study was chemotherapy completion rate. Secondary endpoints included overall survival (OS), disease-free survival (DFS), locoregional control (LRC) and distant metastasis–free interval (DMFS), toxicity, and unplanned admissions.Results: In the carbo-5FU cohort (n = 211), 60.2% of the patients completed chemotherapy vs. 76.7% (p < 0.001) of the patients in the cisplatin cohort (n = 223). Univariate analysis showed a higher risk of death in the carbo-5FU cohort [hazard ratio (HR) 1.53, 95% CI, 1.09–2.14, p = 0.01] with a 3-year OS of 65.4 vs. 76.5% for cisplatin. OS was independently associated with T and N stage and p16 status, but not with chemotherapy regimen (HR 1.08, 95% CI, 0.76–1.55, p = 0.65). Three-year DFS was 70.0% for carbo-5FU vs. 78.6% for cisplatin (HR 1.37, 95% CI, 0.93–2.01, p = 0.05). A similar outcome was observed for both LRC (HR 1.27, 95% CI, 0.74–2.09, p = 0.4) and DMFS (HR 1.08, 95% CI 0.62–1.90, p = 0.77). The risk of discontinuation for chemotherapy-associated toxicity was higher in the carbo-5FU cohort than in the cisplatin cohort (relative risk = 1.69).Conclusion: LA-HNSCC patients treated with concomitant carbo-5FU completed chemotherapy less frequently than patients treated with cisplatin. Treatment regimen was not an independent prognostic factor for OS.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common type of cancer worldwide, accounting for 600,000 new cases and 250,000 cancer deaths each year [1, 2]
Univariate analysis showed a higher risk of death in the carbo-5FU cohort [hazard ratio (HR) 1.53, 95% CI, 1.09–2.14, p = 0.01] with a 3-year overall survival (OS) of 65.4 vs. 76.5% for cisplatin
OS was independently associated with T and N stage and p16 status, but not with chemotherapy regimen (HR 1.08, 95% CI, 0.76–1.55, p = 0.65)

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common type of cancer worldwide, accounting for 600,000 new cases and 250,000 cancer deaths each year [1, 2]. Concomitant CRT consisting of three cycles of high-dose cisplatin on day 1, day 22, and day 43 in combination with 70 Gray (Gy) radiotherapy in 35 fractions is considered the standard of care. This regimen causes significant acute and late toxicity. Concomitant carboplatin plus 5-fluorouracil (carbo-5FU) has been shown to improve OS compared to radiotherapy alone and is an accepted treatment regimen [4]. Chemoradiotherapy (CRT) including three cycles of cisplatin is considered the standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). We compared tolerability and efficacy of concomitant carbo-5FU and cisplatin

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