404O - A phase III prospective randomised trial of two- weekly TPF(Taxane/Platinum/5FU) vs three weekly TPF as induction chemotherapy in locally advanced squamous cell carcinoma of head and neck: A preliminary analysis

Background

Three-weekly TPF has been an effective chemotherapy regimen for locally advanced head and neck squamous cell carcinoma (HNSCC). However, it is associated with a high incidence of neutropenia (77%-80%) and febrile neutropenia (5%-12%). To address this, we conducted a phase III prospective trial comparing the efficacy and safety of two-weekly TPF (2wTPF) with three-weekly TPF (3wTPF).

Methods

Patients with locally advanced HNSCC, with primary tumors in the oral cavity, oropharynx, or hypopharynx, classified as stage III, IVA, or IVB, were randomized in a 1:1 ratio into two arms. The two-weekly arm received Docetaxel 50 mg/m², Cisplatin 50 mg/m², 5-fluorouracil (5-FU) 2500 mg/m² (24-hour infusion), and Leucovorin 250 mg/m² for four cycles. The three-weekly arm received Docetaxel 75 mg/m², Cisplatin 75 mg/m², and 5-FU 750 mg/m² over six hours (day 1-day 4) for three cycles. The primary endpoint was overall survival and secondary end points were PFS, response rate and toxicity profile. This was followed by definitive treatment with either chemo-radiotherapy or surgery.

Results

In this preliminary analysis, 102 patients were recruited from December 2023 to June 2024. Of these, 22 were still on chemotherapy, and 5 were lost to follow-up. The stage distribution was 52%-IVB, 45%-IVA, and 4%-III. Among the 75 patients analyzed (2wTPF: 38, 3wTPF: 37), the overall response rate (ORR) was 76% with 2wTPF (CR=5%, PR=71%, SD=5%) compared to 48% with 3wTPF (CR=0%, PR=48%, SD=18%) (p=0.013). Seven patients (18%) progressed on 2wTPF, while 12 (32%) progressed on 3wTPF (p=0.02). The three-weekly regimen had higher grade 3/4 neutropenia (p=0.03), diarrhea (p=0.03), and infections (p=0.04), with more dose reductions (43% vs. 21%, p=0.05) and delays in chemotherapy (32% vs. 13%, p=0.04). More patients in the 2wTPF arm underwent surgery (23% vs. 13%, p=0.5). Three patients died in each arm, with one death per arm due to treatment-related causes. PFS and OS data remains immature.

Conclusions

The two-weekly TPF regimen demonstrated significantly better response rates and lower toxicity compared to the three-weekly TPF regimen, making it a viable alternative in high-prevalence countries like India.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.