The evidence supporting this protocol is provided by the JCOG1008 trial, a phase II/III randomised controlled trial that was designed to confirm the non-inferiority of weekly cisplatin in patients with post-operative high-risk locally advanced squamous cell carcinoma (SCC) of the head and neck which included: histologically proven SCC in the resected specimen; primary lesion located in the oral cavity, oropharynx, hypopharynx, or larynx; pathologic stages III, IVA, or IVB; high-risk factors for recurrence (microscopically positive margin and/or extranodular extension).r
Between October 2012 and December 2018, 132 patients were randomised to 3-weekly cisplatin (100 mg/m2 every 3 weeks for 3 cycles during the radiation therapy (RT) period or once within 14 days from the day of completion of RT) and 129 patients were randomised to weekly cisplatin (40 mg/m2 every week for 7 cycles) together with concurrent radiation therapy.
The primary end point of the phase III component was overall survival (OS) and secondary end points were relapse-free survival (RFS), local relapse-free survival, nutrition support-free survival, non-hospitalised treatment period during the permissible treatment period and adverse events.
Efficacy
After a median follow-up of 2.2 years (interquartile range [IQR] 1.19-3.56 years) weekly cisplatin was non-inferior to 3-weekly cisplatin chemoradiation therapy for OS (HR=0.69, 99.1% CI: 0.37-1.27; one-sided P for non-inferiority = 0.0027).r Subgroup analysis favoured the weekly arm.
(A) Kaplan-Meier curve for OS (B) unstratified HRs for deathr
©J Clin Oncol 2022
For the secondary endpoint of RFS 88 (33.7%) patients experienced recurrence, 51 patients in the 3-weekly arm and 37 patients in the weekly arm, HR of RFS was 0.71 (95%CI: 0.48-1.06). The HR for local relapse-free survival was 0.73 (95%CI: 0.47-1.13).
Toxicity
Grade 3 or more neutropenia was less frequent in the weekly arm compared to the 3-weekly arm (35% vs 49%).r Thrombocytopenia of any grade was less frequent in the 3-weekly arm compared to the weekly arm (66% vs 84%).
Acute adverse events in ≥15% of patientsr
©J Clin Oncol 2022