Phase II Trial of Neoadjuvant Docetaxel/Cisplatin/5-Fluorouracil Combined with Pegteograstim for Unresectable, Locally Advanced Sinonasal Squamous Cell Carcinoma: KCSG HN18-07

Abstract

Purpose: The role of neoadjuvant chemotherapy in locally advanced sinonasal squamous cell carcinoma (SNSCC) has not been established prospectively. We conducted a phase II trial of neoadjuvant chemotherapy (NAC) with docetaxel/cisplatin/5-fluorouracil (TPF) in this population.

Materials and methods: Eligible patients had unresectable, locally advanced SNSCC, defined as T3/4 category or potential compromise of critical organ function on surgery. Three TPF (docetaxel 75 mg/m2 and cisplatin 75 mg/m2 on day 1, 5-fluorouracil 1,000 mg/m2 on days 1-4 every 3 weeks) cycles were administered with prophylactic pegteograstim. The primary outcome was the objective response rate (ORR); the secondary outcomes included 2-year progression-free survival (PFS), eyeball preservation rate, and safety.

Results: Among 28 patients screened, 25 were evaluable for efficacy (one screen-failure; two evaluable for safety only). The confirmed ORR was 72.0%. The definitive post-NAC treatment comprised chemoradiotherapy (n=15) and surgery (n=10). With a median follow-up of 25.5 months, median PFS was not reached and the 2-year PFS rate was 60.4%. Response to NAC was related to prolonged PFS (p=0.038). No patient underwent eyeball exenteration at the data cutoff point. Treatment-related adverse events of grade ≥ 3 were neutropenia (48.1%) including febrile neutropenia (14.8%), followed by acute kidney injury (22.2%), nausea/vomiting (11.1%), anemia (7.4%), thrombocytopenia (7.4%), and enterocolitis (3.7%).

Conclusion: TPF NAC showed a promising efficacy and might help preserve critical structures in this population, which needs to be validated in a large prospective trial (KCT0003377).

Keywords: Nasal cavity; Neoadjuvant chemotherapy; Paranasal sinus; Prognosiss; Squamous cell carcinoma.

Fig. 1.

CONSORT study diagram. CRT, chemoradiotherapy; NAC, neoadjuvant chemotherapy.

Fig. 2.

Waterfall plot of maximum percent change in the sum of target lesions from baseline according to Response Evaluation Criteria in Solid Tumor ver. 1.1; each bar represents a patient. CR, complete response; CRT, chemoradiotherapy.

Fig. 3.

Kaplan-Meier curves for progression-free survival in total population (A), in evaluable population (n=25) by neoadjuvant chemotherapy response (B), and by type of definitive treatment (C). CR, complete response; CRT, chemoradiotherapy; PD, progressive disease; PR, partial response; SD, stable disease.

Fig. 4.

A case of a T4b maxillary sinus cancer patients treated with docetaxel/cisplatin/5-fluorouracil (TPF) neoadjuvant chemotherapy (NAC) followed by chemoradiotherapy (CRT). (A) Magnetic resonance imaging at diagnosis, after completion of three cycles of NAC, and 4-year follow up after CRT. (B) Radiation field and normal tissue dose before and after NAC.