Dose-dense TPF induction chemotherapy for locally advanced head and neck cancer: a phase II study

Ching-Yun Hsieh, Ming-Yuh Lein, Shih-Neng Yang, Yao-Ching Wang, Yin-Jun Lin, Chen-Yuan Lin, Chun-Hung Hua, Ming-Hsul Tsai, Ching-Chan Lin, Ching-Yun Hsieh, Ming-Yuh Lein, Shih-Neng Yang, Yao-Ching Wang, Yin-Jun Lin, Chen-Yuan Lin, Chun-Hung Hua, Ming-Hsul Tsai, Ching-Chan Lin

Abstract

Background: Phase 3 studies suggest that induction chemotherapy (ICT) of cisplatin and 5-fluorouracil plus docetaxel (TPF) is effective but toxic for patients with squamous-cell carcinoma of the head and neck (SCCHN). Dose-dense chemotherapy may yield favorable outcomes compared with standard-dose chemotherapy, yet the optimal induction regimen remains undefined. We assessed the efficacy and tolerability of biweekly dose-dense TPF ICT in patients with SCCHN.

Methods: In this prospective phase II study, We enrolled patients with stage III/IV (AJCC 7th edition) unresectable squamous cell carcinoma of head and neck cancer. Patients received dose-dense TPF (ddTPF) with cisplatin and docetaxel 50 mg/m2 on day 1, leucovorin 250 mg/m2 on day1, followed by 48-h continuous infusion of 2500 mg/m2 of 5-fluorouracil on day 1 and 2, every 2 weeks for 6 cycles followed by radiotherapy. The primary endpoint was the response rate (RR) after ICT.

Results: Fifty-eight patients were enrolled from June 2014 to September 2015. Overall RR after ICT was 89.6% [complete response (CR), 31%; partial response (PR), 58.6%]. Grade 3/4 neutropenia, mucositis, and diarrhea incidences were 25.9, 1.7, and 1.7%, respectively. 94.8% of patients completed all treatment courses of ICT without dose reduction. The 3-year overall survival (OS) was 54.3% (95%CI: 39.7 to 66.8%) and progression-free survival (PFS) was 34.3% (95%CI: 22.0 to 46.9%). Multivariate analysis showed that CR after ICT is an independent prognostic factor for OS and PFS.

Conclusions: Six cycles of ddTPF is an active, well-tolerated induction regimen for patients with SCCHN. The presence of CR after ICT predicted long-term survival.

Trial registration: ClinicalTrials.gov Identifier: NCT04397341 , May 21, 2020, retrospectively registered.

Keywords: Cisplatin; Docetaxel; Dose-dense chemotherapy; Fluorouracil; Head and neck cancer; Induction chemotherapy.

Conflict of interest statement

The Authors declare that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
Enrollment and outcomes
Fig. 2
Fig. 2
Survival analsysis. a Overall survival. b Progression-free survival. c Local recurrence-free survival. d Metastasis-free survival
Fig. 3
Fig. 3
Survival analysis stratified by response rate (RR) of ICT. a Overall survival. b Progression-free survival. CR: complete response; PR: partial response. ICT: induction chemotherapy

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