Phase II trial of preoperative cisplatin-irinotecan followed by concurrent cisplatin-irinotecan and radiotherapy: PET scan after induction therapy may identify early treatment failure

Abstract

4023 Background: Response on PET scan during preoperative chemotherapy (chemo) for esophageal cancer (EC) has prognostic significance [JCO 19:3058;2001]. Induction chemo with weekly irinotecan(I)/cisplatin(C) relieves dysphagia, and weekly I/C administered with radiotherapy (RT) is well tolerated [ProcASCO 23:Abs 4017;2005]. We completed a Phase II trial of induction I/C followed by I/C/RT followed by surgery. Repeat PET scan was performed after induction chemo and prior to RT. Methods: Patients (pts) with resectable EC/GE junction carcinoma were staged with EUS, PET, and CT scan. Induction chemo consisted of I-65 mg/m2 and C-30 mg/m2 weeks 1,2,4,5, and weeks 7,8,10,11 with RT (180 cGy daily fractions to 5040 cGy). PET scan was repeated at week 6. Esophagectomy was planned 4–8 weeks after RT. Results: 60 pts were enrolled: 6 inevaluable, 54 evaluable, 3 await surgery; 49 male (91%), 5 female (9%), 41 adenocarcinoma (76%), 13 squamous (24%), median age 59, median PS 0, EUS T3N1 35 (65%), N1 40 (74%). Of 41 pts with dysphagia, 31 (76%) had resolution/improvement with induction chemo and 3/54 (6%) required a feeding tube. Of 51 pts, 3 clinical complete responders (CR) deferred surgery (1 refusal, 2 medically inoperable). Of 48 pts, 4 progressed during induction (8%), 9 progressed during RT (19%), and 35 underwent R0 resection (73%). 9/48 (19%) achieved pathologic CR. The median overall survival was 35.4 mos (median follow up 15 mos). In exploratory analysis in 54 pts, response after induction on the week 6 PET scan measured as a decline in SUV, correlated with time to tumor progression (TTP). The mean change in SUV was 43%. A set point of 22% or greater decline in SUV (PET responder) yielded the greatest distinction in TTP (PET responders TTP 18.5 mos, vs nonresponders 5.5 mos, p = 0.03). 4 pts with progression during induction crossed over to RT with paclitaxel: 3 (2 squamous, 1 adenocarcinoma) achieved durable disease control (one pathologic CR, one pathologic PR, one clinical CR). Conclusions: Response on PET scan during induction chemo for EC may identify early treatment failures, and may direct pts to successful salvage with alternative chemo during RT. Supported by a grant from Pfizer. [Table: see text]