First-line chemotherapy with docetaxel, oxaliplatin, and timed-flat infusion 5Fluorouracil in metastatic gastro-esophageal adenocarcinomas: The experience with FD/FOx regimen.

Abstract

178 Background: Triplet chemotherapies, with fluoropyrimidines, platin derivates and Docetaxel, represent an option for first line treatment of metastatic Gastro-Esophageal Adenocarcinoma (mGEA). To increase tolerability and dose intensity (DI), we previously developed an alternative way of administration of 5Fluorouracil (5FU), with nocturnal “timed-flat infusion” (TFI) (from 10:00 PM to 10:00 AM), without 5FU bolus and Folinic Acid, in several combination-schedules in breast and colorectal cancers. Methods: We report a retrospective analysis of 27 mGEA patients (pts) treated with FD/FOx regimen, a schedule of weekly TFI/5FU for two nights at 1000 or 900 mg/m2/night, associated to alternating Docetaxel at 50 mg/m2 on days 1 and 15, and Oxaliplatin at 80 mg/m2 on days 8 and 22, cycles repeated every 4 weeks. Results: From June 2007 to July 2017, 17 pts (62.9%) were treated with standard FD/FOx and 10 pts (37.1%) with modified FD/FOx (defined by any projected dose reduction compared to standard) due to age, PS and comorbidities. Median age was 60 years (range 41-80), male/female ratio 19/8, ECOG-PS 0, 7 (26%), 1, 16 (59%), 2, 4 (15%); 17 pts (62.9%) had a Cumulative Illness Rating Scale Intermediate stage, 1 patient (3.7%) a Secondary one. Thirteen pts (48%) had unresected primary tumor. ORR, median PFS and median OS were 73.9% (α0.05, CI±18), 13 and 16 months, respectively. The only G4 toxicity was neutropenia (11.1%); G3 were: neutropenia (29.6%), asthenia (22.2%), diarrhea (22.2%); most relevant G2 toxicities were: nausea (33.3%), anorexia (40.7%), neuropathy (37.0%) and anemia (40.7%). No febrile neutropenia was observed. The received (r)DI were 80% of standard full dose of each drug: Docetaxel 20 mg/m2/week, Oxaliplatin 32 mg/m2/week and 5FU 1440 mg/m2/week. Out of 21 pts who progressed to FD/FOx, 13 pts (48.1%) underwent a second line therapy (6 rechallenges with taxanes). Conclusions: Even if requires a careful management, FD/FOx is a feasible option for first line treatment of mGEA pts, particularly in needing of tumor shrinkage, with significant activity, high rDIs, and acceptable safety profile when compared to literature.