Once-Weekly vs Every-3-Week Cisplatin Chemoradiation in Locally Advanced Head and Neck Cancer

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Vanita Noronha, MD

Vanita Noronha, MD

In an Indian phase III trial reported in the Journal of Clinical Oncology, Vanita Noronha, MD, of Tata Memorial Hospital, Mumbai, and colleagues found that curative-intent adjuvant chemoradiation with cisplatin at 100 mg/m2 every 3 weeks produced better locoregional control vs cisplatin at 30 mg/m2 every week in patients with locally advanced head and neck squamous cell cancer.1 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 receive 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 feature (eg, extracapsular extension, close [≤ 5 mm] or positive margins, ≥ 2 positive nodes, or T4 primary disease) or for definitive adjuvant chemoradiation for unresectable disease or organ preservation.

The primary endpoint was locoregional control. The database was locked in May 2017.

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 adjuvant chemoradiation in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative 2-year locoregional control rate was 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).

Once-every-3-weeks cisplatin at 100 mg/ m2 … should remain the preferred chemoradiotherapy regimen for [locally advanced head and neck squamous cell cancer] in the adjuvant setting.

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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 adverseevents 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).


  • A once-every-3-week cisplatin regimen produced better locoregional control vs a once-weekly
    lower-dose regimen.
  • Severe adverse events were more common with the every-3-week regimen.

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.”

DISCLOSURE: The study was funded by the Tata Memorial Center Research Administration Council. The study authors reported no conflicts of interest.


1. Noronha V, Joshi A, Patil VM, et al: Once-a-week versus once-every-3-weeks cisplatin chemoradiation for locally advanced head and neck cancer: A phase III randomized noninferiority trial. J Clin Oncol 36:1064-1072, 2018.