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

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/m 2 at day 1, 22, and 43 followed by 5FU 600 mg/m 2 /day for 96 h. The other center used cisplatin 100 mg/m 2 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, Hanemaaijer et al. Carboplatin+5-Fluorouracil vs. Cisplatin for HNSCC 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.

Deciphering the Genetic Alterations in SPARC Gene Family and Its Association with HNSCC

“…Head and neck cancers have globally affected more than 5.5 million people and have caused about 379,000 deaths [21]. The majority of the squamous cell carcinomas occur in the head and neck region [22].…”

Ibero-American Expert Consensus on Squamous Cell Carcinoma of the Head and Neck Treatment in Patients Unable to Receive Cisplatin: Recommendations for Clinical Practice

“…In addition, adherence was lower with carboplatin + 5-fluorouracil, possibly because of its higher rates of toxicity. 50 A meta-analysis also showed that OS was shorter with carboplatin than with cisplatin, with more hematologic toxicity and mucositis. 51 …”

“…In addition, adherence was lower with carboplatin + 5-fluorouracil, possibly because of its higher rates of toxicity. 50 A meta-analysis also showed that OS was shorter with carboplatin than with cisplatin, with more hematologic toxicity and mucositis. 51 Clinical evidence supporting the cetuximab use as an alternative to cisplatin in locally advanced disease was provided by a phase III study, in which the use of radiotherapy with or without cetuximab was evaluated.…”

Comparison of efficacy and toxicity of chemoradiation regimens for head and neck squamous cell carcinoma primary treatment

“…Superior OS was reported with CRT using cisplatin as compared to using Cetuximab 15,16 . Treatment with cisplatin was found to result in survival outcomes that are comparable to those with carboplatin in some studies, 8,10,26 but to be superior to carboplatin in others, whether the latter was used alone 27 or with 5‐FU 28 . Compared to CRT with LDC, CRT with HDC was reported to have either greater 1,3,11,24 or comparable 13 toxicity profile, or even lower acute toxicity 21 .…”