Sequential chemoradiotherapy (SCRT) for larynx preservation (LP): Preliminary results of the randomized phase II TREMPLIN study

Abstract

6010 Background: Induction chemotherapy (ICT) followed by irradiation (RT) and concurrent chemoradiotherapy (CRT) are validated options for LP. Docetaxel-based ICT, concurrent cetuximab and RT are new options and SCRT (ICT followed by CRT) has been reported as a potential new approach. However, to date there are no data assessing SCRT specifically for LP. Methods: Previously untreated patients (pts) with larynx or hypopharynx squamous cell carcinoma and candidates for a total laryngectomy were eligible for this randomized phase II study. Eligible pts received 3 cycles of ICT (docetaxel and cisplatin both 75 mg/m2 on day 1 and 5-FU 750 mg/m2/day on days 1–5). In case of response ≥ 50 % pts were randomized to receive either in arm A: RT (70 Gy) with cisplatin (100 mg/m2 on days 1, 22 and 43 of RT) or in arm B: Cetuximab (400 mg/m2 loading dose before RT and 250 mg/m2 on the first day of the 7 weeks of RT. Pts with response < 50% had salvage surgery. Primary endpoint was LP 3 months after treatment, secondary endpoints were larynx function preservation at 18 months, quality of function and tolerance to treatment. Results: From March 2006 to April 2008 (end of accrual), 153 pts with stage III-IV larynx/hypopharynx cancer were enrolled in the study and could start ICT. Of them 74 % could receive the planned ICT while the others had either reduced dosages or less than 3 cycles. Toxic deaths occurred in 3 pts (2%). Of the 147 evaluable pts after ICT, 22 were non-responders (15%), 4 pts were withdrawn from the study, 6 responding pts with ICT-related toxicity precluding any further cisplatin could not be randomized and finally 115 pts could be randomized (59 in arm A and 56 in arm B). 3 months after treatment there was no significant difference in LP (93% in arm A and 96% in arm B). In arm A, 45 % of pts could receive the full CRT protocol vs 71 % in arm B. In arm A 50% of pts had cisplatin-related toxicity (definitive in 52% the cases) while in arm B 26 % of patients had cetuximab-related toxicity (definitive in only 1 case). There was no CRT treatment-related death. Conclusions: SCRT is considered for LP. ICT followed by RT with concurrent cetuximab appeared better tolerated than with concurrent cisplatin with the same LP rate 3 months after treatment. [Table: see text]