Comparative meta-analysis of cisplatin dosing schedules in definitive chemoradiotherapy for locoregionally advanced head and neck squamous cell carcinoma.

Abstract

e18063 Background: Cisplatin-based chemoradiotherapy is the standard for locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC), but the optimal dosing schedule remains unclear. This meta-analysis compares weekly, three-weekly, and other cisplatin regimens. Methods: A meta-analysis of 21 clinical trials evaluated definitive cisplatin-based chemoradiotherapy in LAHNSCC. Patients received weekly cisplatin (35–40 mg/m²), three-weekly cisplatin (100 mg/m²), or other regimens, including daily or intra-arterial schedules. Outcomes included survival, locoregional control, mortality, and toxicities. A random-effects model calculated pooled proportions with 95% confidence intervals. Results: In the weekly cisplatin group (n=3,969), completion rates ranged from 67–99%. Pooled overall survival (OS) was 71.83% (95% CI: 52.25–85.60%), median 36 months. Progression-free survival (PFS) was 68.50% (95% CI: 44.16–85.67%), median 26 months. Locoregional control (LRC) was 83.82% (95% CI: 68.38–92.55%). Mortality was 20.74%, with dysphagia (48.85%), xerostomia (14.15%), and ototoxicity (6.94%) common. In the three-weekly group (n=1,903), completion rates ranged from 38–100%. OS was 56.47% (95% CI: 31.89–78.24%), median 21.6 months. PFS was 51.06% (95% CI: 47.23–54.88%), median 12.45 months. LRC was 67.34% (95% CI: 63.31–71.14%). Mortality was 34.67%, with higher rates of dysphagia (63.02%) and xerostomia (47.06%). In the other schedules group (n=210), completion rates were 90–94%. OS was 50.53% (95% CI: 43.33–57.70%), with mortality at 47.65%. Dysphagia (63.23%), hypothyroidism (20%), and ototoxicity (10.13%) were common. Conclusions: Weekly cisplatin achieved the highest survival and locoregional control with better adherence. Three-weekly dosing had lower survival and more late toxicities, while other schedules showed the highest mortality. Weekly dosing appears most favorable in efficacy and safety. Meta-analytical findings. Parameter Weekly 3-Weekly Other Schedules Cisplatin Dose 35–40 mg/m² weekly 100 mg/m² every 3 wks 6 mg/m² daily or 100–150 mg/m² intra-arterial Radiotherapy Dose 55–70 Gy/4–7 weeks 66–70 Gy/6–7 weeks 70 Gy/6–7 weeks Completion Rate 67–99 38–100 90–94 OS 71.83 (52.25–85.60) 56.47 (31.89–78.24) 50.53 (43.33–57.70) PFS 68.50 (44.16–85.67) 51.06 (47.23–54.88) 33.06 (24.78–42.19) LRC 83.82 (68.38–92.55) 67.34 (63.31–71.14) 55.37 (46.06–64.41) Mortality 20.74 (8.38–42.82) 34.67 (12.38–66.59) 47.65 (40.55–54.84) Acute Toxicities 62.34 (50.31–73.02) 58.34 (40.64–74.13) NR Late Toxicities 12.11 (8.92–16.24) 17.46 (14.64–20.68) NR