Metformin Use During Treatment of Potentially Curable Esophageal Cancer Patients is not Associated with Better Outcomes.
BACKGROUND
Metformin use has been associated with a dose-dependent increased response to neoadjuvant chemo(radio)therapy in esophageal cancer patients. However, no association between metformin use and overall survival has been reported yet. The purpose of our study was to investigate the effect of metformin use on pathological response as well as overall and disease-free survival in patients with resectable esophageal cancer.


METHODS
Between March 1994 and September 2013, all patients undergoing an esophagectomy for esophageal and gastroesophageal junction cancer after neoadjuvant chemo(radio)therapy with curative intent were included in a prospective database. A complete pathological response was defined as ypT0N0M0, Mandard 1. Kaplan-Meier curves with log-rank testing were performed for overall survival and disease-free survival.


RESULTS
A total of 461 patients were included with a median follow-up of 24 months (range 1-228); 43 patients were diagnosed with diabetes mellitus type II (9.3 %) of whom 32 patients used metformin (74 %). A total of 94 (20 %) patients had a complete pathological response, which did not differ between metformin users (19 %) and non-metformin users (21 %, p = 0.99). We did not observe a statistically significant difference between metformin users and non-metformin users for median overall survival (43.6 vs. 42.8 months, p = 0.66) or for median disease-free survival (31.1 vs. 47.0 months, p = 0.68). A subgroup analysis in patients with diabetes mellitus type II showed a nonsignificant increase in median overall survival for metformin users (43.6 months) compared with non-metformin users (21.4 months, p = 0.44). For median disease-free survival, a similar nonsignificant increase was observed for metformin users (31.1 months) compared with non-metformin users (20.1 months, p = 0.31).


CONCLUSIONS
The use of metformin did not result in higher pathological response rates or improved overall survival or disease-free survival compared with non-metformin use in patients receiving neoadjuvant chemo(radio)therapy for resectable esophageal cancer. In contrast to what has been postulated for other tumor types, metformin may not have a beneficial effect in esophageal cancer.
Department of Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands.
L E A M M
LE
Spierings
Department of Surgical Oncology, Academic Medical Centre, Amsterdam, The Netherlands.
S M
SM
Lagarde
Department of Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands.
M G H
MG
van Oijen
Department of Surgical Oncology, Academic Medical Centre, Amsterdam, The Netherlands.
S S
SS
Gisbertz
Department of Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands.
J W
JW
Wilmink
Department of Radiation Oncology, Academic Medical Centre, Amsterdam, The Netherlands.
M C C M
MC
Hulshof
Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands.
S L
SL
Meijer
Department of Surgical Oncology, Academic Medical Centre, Amsterdam, The Netherlands.
M C
MC
Anderegg
Department of Surgical Oncology, Academic Medical Centre, Amsterdam, The Netherlands.
M I
MI
van Berge Henegouwen
Department of Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands. h.vanlaarhoven@amc.nl.
H W M
HW
van Laarhoven
D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality* / Q000556:secondary; D059248:Chemoradiotherapy / Q000401:mortality; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D016629:Esophagectomy / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000401:mortality; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D016879:Salvage Therapy; D015996:Survival Rate
D007004:Hypoglycemic Agents; D008687:Metformin; D016190:Carboplatin; D017239:Paclitaxel