In a Japanese phase II/III trial (JCOG1008) reported in the Journal of Clinical Oncology, Kiyota et al found that overall survival with once-weekly cisplatin in postoperative chemoradiation was noninferior to every-3-week cisplatin for patients with high-risk locally advanced squamous cell carcinoma of the head and neck.
Study Details
In the multicenter open-label trial, 261 patients were randomly assigned between October 2012 and December 2018 to receive chemoradiation with cisplatin at 40 mg/m2 once a week for seven cycles (n =129) or 3-weekly cisplatin at 100 mg/m2 for three cycles. The primary endpoint was overall survival; noninferiority of weekly cisplatin would be concluded if the upper limit of the 99.1% confidence interval of the hazard ratio was ≤ 1.32.
Overall Survival
At third interim analysis, with a median follow-up of 2.2 years (interquartile range = 1.19–3.56 years), death had occurred in 25% of patients in the weekly group vs 33% of patients in the 3-weekly group (hazard ratio [HR] = 0.69, 99.1% confidence interval [CI] = 0.374–1.273, P = .0027 for noninferiority). Estimated survival rates were 77.7% vs 74.2% at 2 years and 71.6% vs 59.1% at 3 years.
Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk locally advanced squamous cell carcinoma of the head and neck. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients.— Kiyota et al
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Recurrence was observed in 37 patients in the weekly group vs 51 in the 3-weekly group. The hazard ratio for recurrence-free survival was 0.71 (95% CI = 0.48–1.06); the hazard ratio for local relapse–free survival was 0.73 (95% CI = 0.47–1.13).
Adverse Events
Grade ≥ 3 adverse events occurred in 81.1% of patients in the weekly cisplatin group vs 79.8% of the 3-weekly group (P = .87). Grade ≥ 3 neutropenia (35% vs 49%) and infection (7% vs 12%) were less common in the weekly cisplatin group. Among other grade ≥ 3 adverse events, leukocytopenia occurred in 62% vs 55%, mucositis in 28% vs 23%, and dysphagia in 12% vs 19%. Any-grade renal impairment occurred in 30% vs 40% and any-grade hearing impairment occurred in 17% vs 7%. Treatment-related death occurred in no patients in the 3-weekly group and in two patients (1.6%) in the weekly group, due to febrile neutropenia and laryngeal edema.
The investigators concluded, “Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk locally advanced squamous cell carcinoma of the head and neck. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients.”
Makoto Tahara, MD, PhD, of the Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Chiba, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by National Cancer Center Research and Development Funds, a grant from the Ministry of Health Labor and Welfare of Japan, and others. For full disclosures of the study authors, visit ascopubs.org.
