Publication details

Weekly Low-Dose Versus Three-Weekly High-Dose Cisplatin for Concurrent Chemoradiation in Locoregionally Advanced Non-Nasopharyngeal Head and Neck Cancer: A Systematic Review and Meta-Analysis of Aggregate Data

Authors

SZTURZ Petr WOUTERS K. KIYOTA N. TAHARA M. PRABHASH K. NORONHA V. CASTRO A. LICITRA L. ADELSTEIN D. VERMORKEN J.B.

Year of publication 2017
Type Article in Periodical
Magazine / Source ONCOLOGIST
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1634/theoncologist.2017-0015
Keywords Head and neck cancer; Radiotherapy; Cisplatin; Toxicity; Survival
Description Background. Three-weekly high-dose cisplatin (100 mg/m(2)) is considered the standard systemic regimen given concurrently with postoperative or definitive radiotherapy in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, due to unsatisfactory patient tolerance, various weekly low-dose schedules have been increasingly used in clinical practice. The aim of this meta-analysis was to compare the efficacy, safety, and compliance between these two approaches. Materials and Methods. We systematically searched literature for prospective trials of patients with LA-SCCHN who received postoperative or definitive conventionally fractionated concurrent chemoradiation. Radiation doses were usually 60-66 gray (Gy) in the postoperative setting and 6670 Gy in the definitive setting. Standard, three-weekly high-dose cisplatin (100 mg/m(2), 3 doses) was compared with the weekly low-dose protocol (<50 mg/m(2), >6 doses). The primary endpoint was overall survival. Secondary outcomes comprised response rate, acute and late adverse events, and treatment compliance. Results. Fifty-two studies with 4,209 patients were included in two separate meta-analyses according to the two clinical settings. There was no difference in treatment efficacy as measured by overall survival or response rate between the chemoradiation settings with low-dose weekly and high-dose three-weekly cisplatin regimens. In the definitive treatment setting, the weekly regimen was more compliant and significantly less toxic with respect to severe (grade 3-4) myelosuppression (leukopenia p = .0083; neutropenia p = .0024), severe nausea and/or vomiting (p < .0001), and severe nephrotoxicity (p = .0099). Although in the postoperative setting the two approaches were more equal in compliance and with clearly less differences in the cisplatin-induced toxicities, the weekly approach induced more grade 3-4 dysphagia (p = .0026) and weight loss (p < .0001). Conclusion. In LA-SCCHN, current evidence is insufficient to demonstrate a meaningful survival difference between the two dosing regimens. Prior to its adoption into routine clinical practice, the low-dose weekly approach needs to be prospectively compared with the standard three-weekly high-dose schedule.

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