Comparison of Chemoradiation Treatment Schedules in Locally Advanced Head and Neck Cancer
In an Indian phase III trial reported in the Journal of Clinical Oncology, Noronha and colleagues found that curative-intent adjuvant chemoradiotherapy with cisplatin at 100 mg/m2 every 3 weeks produced better locoregional control than cisplatin at 30 mg/m2 every week in patients with locally advanced head and neck squamous cell cancer. Severe adverse events were more common in the every-3-week group.
Study Details
In the noninferiority trial, 300 patients with locally advanced head and neck cancer at Tata Memorial Center in Mumbai were randomized between 2013 and 2017 to cisplatin at 30 mg/m2 given once a week (n = 150) vs cisplatin at 100 mg/m2 given once every 3 weeks (n = 150), both administered concurrently with curative-intent radiotherapy. Disease had to be locally advanced with no distant metastases with planned curative chemoradiation, either as adjuvant treatment for ≥ 1 high-risk features (eg, extracapsular extension, close [≤ 5 mm] or positive margins, ≥ 2 positive nodes, or T4 primary disease) or for definitive chemoradiotherapy for unresectable disease or organ preservation. The primary endpoint was locoregional control. The data base was locked in May 2017.
Overall, patients had a median age of 44 years; 89% were male; 9% had no history of tobacco use; the oral cavity was the primary site in 87% of patients; histology was moderately differentiated in 56%; 61% had T4 disease; 70% had N2 disease; and 91% had stage IV disease. All patients received conventional external-beam radiotherapy; the median radiation dose was 60 Gy delivered in a median of 30 fractions over a median of 44 days.
Locoregional Control
In total, 279 patients (93%) received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22 months, estimated cumulative 2-year locoregional control rates were 73.1% in the every-3-week group vs 58.5% in the once-weekly group (absolute difference = 14.6%, 95% confidence interval [CI] = 5.7%–23.5%; upper bound > 15%, indicating absence of noninferiority). The hazard ratio (HR) significantly favored the every-3-week group at 1.76 (P = .014).
Estimated median progression-free survival was 28.6 months (95% CI = 15.90–41.30 months) vs 17.7 months (95% CI = 0.42–35.05 months; HR = 1.24, P = .21). Estimated median overall survival was not reached vs 39.5 months (HR = 1.14, P = .48).
Adverse Events
Acute adverse events of grade ≥ 3 occurred in 85% of the every-3-week group vs 72% of the once-weekly group (P = .006), with the most common being lymphopenia (89% vs 72%), dysphagia (39% vs 42%), and odynophagia (52% vs 41%). Hospitalization for toxicity occurred in 31.1% vs 13.3% (P < .001). Feeding tube placement was required in 68% vs 66% (P = .68). Among 126 patients in the every-3-week group and 116 in the once-weekly group evaluated for chronic toxicity, grade ≥ 3 toxicity occurred in 13.5% vs 10.3% (P = .55).
The investigators concluded, “Once-every-3-weeks cisplatin at 100 mg/m2 resulted in superior [locoregional control], albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m2, and should remain the preferred chemoradiotherapy regimen for [locally advanced head and neck squamous cell cancer] in the adjuvant setting.”
The study was funded by the Tata Memorial Center Research Administration Council.
Kumar Prabhash, MD, DM, of Tata Memorial Hospital, Mumbai, is the corresponding author for the Journal of Clinical Oncology article.
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