Comparison of Carboplatin With 5-Fluorouracil vs. Cisplatin as Concomitant Chemoradiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma
Saskia H. Hanemaaijer, Iris C. Kok, Rudolf S.N. Fehrmann, Bert van der Vegt, Jourik A. Gietema, Boudewijn E. C. Plaat, Marcel A.T.M. van Vugt, Marije R. Vergeer, C. René Leemans, Johannes A. Langendijk, Jens Voortman, Jan Buter, Sjoukje F. Oosting
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 due to 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. Material 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 600mg/m2/day for 96 hours. 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 versus 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 (HR 1.53, 95% CI, 1.09 - 2.14, p = 0.01) with a three-year OS of 65.4% versus 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 versus 78.6% for cisplatin (HR = 1.37, 95% CI, 0.93 - 2.01, p = 0.05). 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.