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

Abstract

Given concurrently with conventional radiotherapy in locally advanced head and neck cancer, high-dose three-weekly cisplatin has often been replaced with weekly low-dose infusions to increase compliance and decrease toxicity. The present meta-analysis suggests that both approaches might be equal in efficacy, both in the definitive and postoperative settings, but differ in toxicity. However, some toxicity data can be influenced by unbalanced representation, and the conclusions are not based on adequately sized prospective randomized studies. Therefore, low-dose weekly cisplatin should not be used outside clinical trials but first prospectively studied in adequately sized phase III trials versus the high-dose three-weekly approach.

Comparing high‐dose cisplatin with cisplatin‐based combination chemotherapy in definitive concurrent chemoradiation setting for locally advanced head and neck squamous cell carcinoma (LAHNSCC)

“…Three‐weekly single agent high‐dose cisplatin is considered as the standard of care systemic therapy for definitive concurrent chemoradiation setting. Despite the irrefutable benefits, higher incidence of severe acute toxicities (16%‐47%) and relatively low compliance rates (60%‐70%) raise significant concern regarding tolerability of this regimens in the minds of treating physicians and patients . In addition, long‐term follow‐up of RTOG91‐11 discovered significantly higher non‐cancer‐related mortality in patients who received high‐dose cisplatin concomitantly with radiation .…”

“…Consequently, there has been an effort to reduce the treatment‐related complications without compromising anticancer activity. Weekly low dose cisplatin (30‐40mg/m2) is considered an alternative option to high dose cisplatin as it offers similar dose intensity, reduces chemotherapy‐related acute adverse events, and facilitates dose adjustments according to changes in patient's condition with relatively similar survival benefit as suggested by a meta‐analysis . Nevertheless, other studies have questioned this finding.…”

Role of adjuvant chemoradiotherapy in T4N0 stage IV head and neck cancer: A National Cancer Database analysis

“…Alternative dosing schedules also exist, in a comparison of low‐dose weekly cisplatin (≤50 mg/m 2 , ≥6 doses) and high‐dose bolus cisplatin (100 mg/m 2 , 3 doses), a meta‐analysis of 52 studies of 4209 patients revealed no difference in treatment efficacy between high‐dose cisplatin compared to low‐dose cisplatin. Although, in the definitive treatment setting, weekly cisplatin was noted to be associated with better compliance and less toxicity with regard to myelosuppression, nephrotoxicity, and severe nausea and vomiting . In a study of 7219 patients with HNSCC, in definitive setting, total cisplatin dose of ≥240 mg/m 2 was found to be an independent prognostic risk factors for OS .…”

Feasibility of Dose-escalated Hypofractionated Chemoradiation in Human Papilloma Virus-negative or Smoking-associated Oropharyngeal Cancer

“…The reduced CTV compared with less conformal techniques in older studies may account for the tolerability of the dose escalation in this study. Further reduction in the CTV may be possible, but higher quality diagnostic and possibly functional imaging may be required [40]. It is also important to recognise that the dose escalation in this study was carried out with daily image guidance and online correction.…”