ABSTRACT
BACKGROUND: The optimal chemotherapy backbone for HER2-negative advanced esophagogastric cancer, either in combination with targeted therapies or as a comparator in clinical trials, is uncertain. The subtle yet crucial differences in platinum-based regimens' safety and synergy with combination treatments need consideration. METHODS: We analyzed cases from the AGAMENON-SEOM Spanish registry of HER2-negative advanced esophagogastric adenocarcinoma treated with platinum and fluoropyrimidine from 2008 to 2021. This study focused exclusively on patients receiving one of the four regimens: FOLFOX (5-FU and oxaliplatin), CAPOX (capecitabine and oxaliplatin), CP (capecitabine and cisplatin) and FP (5-FU and cisplatin). The aim was to determine the most effective and tolerable platinum and fluoropyrimidine-based chemotherapy regimen and to identify any prognostic factors. RESULTS: Among 1293 patients, 36% received either FOLFOX (n = 468) or CAPOX (n = 466), 20% CP (n = 252), and 8% FP (n = 107). FOLFOX significantly increased PFS (progression free survival) compared to CP, with a hazard ratio of 0.73 (95% CI 0.58-0.92, p = 0.009). The duration of treatment was similar across all groups. Survival outcomes among regimens were similar, but analysis revealed worse ECOG-PS (Eastern Cooperative Oncology Group-Performance Status), > 2 metastatic sites, bone metastases, hypoalbuminemia, higher NLR (neutrophil-to-lymphocyte ratio), and CP regimen as predictors of poor PFS. Fatigue was common in all treatments, with the highest incidence in FOLFOX (77%), followed by FP (72%), CAPOX (68%), and CP (60%). Other notable toxicities included neuropathy (FOLFOX 69%, CAPOX 62%), neutropenia (FOLFOX 52%, FP 55%), hand-foot syndrome in CP (46%), and thromboembolic events (FP 12%, CP 11%). CONCLUSIONS: FOLFOX shown better PFS than CP. Adverse effects varied: neuropathy was more common with oxaliplatin, while thromboembolism was more frequent with cisplatin.
Subject(s)
Adenocarcinoma , Antineoplastic Combined Chemotherapy Protocols , Capecitabine , Cisplatin , Esophageal Neoplasms , Fluorouracil , Leucovorin , Oxaliplatin , Receptor, ErbB-2 , Registries , Stomach Neoplasms , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Female , Male , Middle Aged , Aged , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Fluorouracil/therapeutic use , Fluorouracil/administration & dosage , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Capecitabine/therapeutic use , Capecitabine/administration & dosage , Receptor, ErbB-2/metabolism , Leucovorin/therapeutic use , Leucovorin/administration & dosage , Leucovorin/adverse effects , Oxaliplatin/therapeutic use , Oxaliplatin/administration & dosage , Cisplatin/therapeutic use , Cisplatin/administration & dosage , Adult , Organoplatinum Compounds/therapeutic use , Organoplatinum Compounds/administration & dosage , Progression-Free Survival , Esophagogastric Junction/pathology , Aged, 80 and over , SpainABSTRACT
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