Altered fractionation radiotherapy combined with concurrent low-dose or high-dose cisplatin in head and neck cancer: A systematic review of literature and meta-analysis.

OBJECTIVES

Altered fractionation radiotherapy and concomitant chemoradiotherapy represent commonly used intensification strategies in the management of locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). This meta-analysis compares compliance, safety, and efficacy between two single-agent cisplatin schedules given concurrently with altered fractionation radiotherapy.

METHODS

We systematically searched for prospective trials of patients with LA-SCCHN who received post-operative or definitive altered fractionation concurrent chemoradiotherapy. High-dose cisplatin once every three to four weeks (100 mg/m, 2 doses) was compared with a weekly low-dose protocol (≤50 mg/m, ≥4 doses). The primary outcome was overall survival. The secondary endpoints comprised treatment adherence, acute and late toxicities, and objective response rate.

RESULTS

Twelve studies with 1373 patients treated with definitive chemoradiotherapy were included. Compared to the weekly low-dose cisplatin regimen, the three- to four-weekly high-dose cisplatin regimen improved overall survival (p=.0185), was more compliant with respect to receiving all planned cycles of cisplatin (71% versus 95%, p=.0353), and demonstrated less complications in terms of severe (grade 3-4) acute mucositis and/or stomatitis (75% versus 40%, p=.0202) and constipation (8% versus 1%, p=.0066), toxic deaths (4%, versus 1%, p=.0168), 30-day mortality (8% versus 3%, p=.0154), and severe late subcutaneous fibrosis (21% versus 2%, p<.0001). Overall and complete response rates were similar between both chemotherapy schedules.

CONCLUSION

In chemoradiotherapy incorporating altered fractionation, two cycles of high-dose cisplatin with a three to four week interval are superior to weekly low-dose schedules. Further studies should identify those who might derive the greatest benefit from this intensified approach.