Abstract

ABSTRACT Background In the daily clinical practice GC is considered as a single disease. However, preliminary data identified distinct subtypes characterized by relevant differences in epidemiology, carcinogenesis and gene expression profiles. Recently, a new classification has been proposed, based on Lauren's histology and on anatomic tumour location, identifying three subtypes: type 1 (proximal non diffuse GC), type 2 (diffuse GC) and type 3 (distal non diffuse GC). Aim of our analysis was to compare clinical outcome (in terms of response rate, RR, progression-free survival, PFS, and overall survival, OS) according to different GC subtypes (1,2,3) in patients (pts) receiving first-line chemotherapy. Patients and methods Advanced GC pts treated with a first-line combination chemotherapy were included in our analysis. Pts were divided in three subgroups (type 1, type 2 and type 3) as previously defined. Results A total of 202 advanced GC pts were included: most of pts belonged to type 2 (50.5%) and type 3 (40.6%); type 1 included 18 pts (8.9%). The majority of pts (62%) received a three-drugs chemotherapy combinations including a platinum derivate, a fluoropyrimidine with the addition of an anthracycline, a taxane or mytomicin C; the remaining patients received a platinum and fluoropyrimidine combination. The three pts subgroups resulted comparable for relevant clinical factors such as ECOG PS, tumour stage, number of metastatic sites, previous surgical resection, first-line combination and use of second-line treatments; as expected peritoneal carcinosis was more common in type 2 pts. RR was found to be higher in type 3 pts (RR = 45.1%) than in type 1 (27.8%) and type 2 (25.5%) (p = 0.017). Type 2 pts presented a shorter PFS (median PFS 5.7 months) compared to type 1, median PFS = 6.9 months, and type 3, median PFS = 7.8 months (p = 0.0069). These differences did not translate in statistically significant differences in OS. Conclusions Our results suggest that GC subtypes may be important predictors of benefit from chemotherapy in advanced GC patients. Future clinical trials should take in account these differences for a better stratification of patients. Disclosure All authors have declared no conflicts of interest.

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