The Evidence On Effectiveness Of Weekly Versus Tri-Weekly Cisplatin Concurrent With Radiotherapy In Locally Advanced Head And Neck Squamous Cell Carcinoma (HNSCC)

Abstract

Background
This paper aims to synthesize the current available evidences on the effectiveness of weekly versus tri-weekly cisplatin concurrent with radiotherapy in the primary and adjuvant treatment of locally advanced HNSCC. A dose of 100 mg/m2 administered every three weeks with concurrent radiotherapy is the most widely utilized and studied regimen. While triweekly schedule remains the standard of care, some have suggested giving 30-40mg/m2 weekly especially to elderly and patients with low renal reserve, as it is hypothesized to be less toxic, better tolerated and with more radiosensitizing effect without compromising oncologic outcomes.

Methods
A systematic review and meta-analysis of the literature were undertaken to assess the effectiveness of weekly versus triweekly schedule in primary and adjuvant treatment of HNSCC. Search of relevant articles from electronic database from 2000 to March 2016 and appraisal of studies were done.

Results
One randomized controlled trial (RCT) and six retrospective studies were included in this review. The RCT showed less severe mucositis (75% vs. 38.5%, p=0.012) and more patients receiving at least 200mg/m2 (62.5% vs. 88.5%, p=0.047) in triweekly arm. There is no difference in one-year progression-free survival (PFS) (60% vs. 71.1%, p=0.806) and one-year overall survival (OS) (71.6 vs. 79.3%, p=0.978) between the weekly and tri-weekly arm. Pooling of data from six studies showed no difference in 5-year PFS (RR 1.14, 95%, CI=0.94-1.39), 5-year OS (RR 1.15, 95%, CI=0.92-1.45), severe renal events (RR 0.66, 95% CI=0.42-1.04), severe mucositis (RR 0.92, 95%, CI-0.71-1.21), severe dermatitis (RR 0.61, 95%, CI=0.37-1.03), treatment interruptions (RR 1.06, 95%, CI=0.74-1.52) and number of patients receiving at least 200mg/m2 (RR 0.83, 95%, CI=0.67-1.03).

Conclusion
The current evidence showed that weekly schedule is not superior to tri-weekly in improving oncologic outcomes and decreasing early toxicities of treatment. In the absence of compelling data, tri-weekly schedule should still remain the standard of care for concurrent schedule. Most studies included are retrospective in design and more randomized controlled trials are warranted.