title: Anthracycline-based triplets do not improve the efficacy of platinum-fluoropyrimidine doublets in first-line treatment of advanced gastric cancer: real-world data from the AGAMEMON National Cancer Registry.
abstract: BACKGROUND
  Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry.
  
  
  METHODS
  Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression.
  
  
  RESULTS
  A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision.
  
  
  CONCLUSIONS
  Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.
authors.affiliation: Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, IMIB, Avenida Marqués de los Vélez, 30008, Murcia, Spain. alberto.carmonabayonas@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Carmona-Bayonas
authors.affiliation: Medical Oncology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Jiménez-Fonseca
authors.affiliation: Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Custodio
authors.affiliation: Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, IMIB, Avenida Marqués de los Vélez, 30008, Murcia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sánchez Cánovas
authors.affiliation: Medical Oncology Department, Hospital Universitario de Canarias, Tenerife, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Hernández
authors.affiliation: Medical Oncology Department, Corporació Sanitària Parc Taulí , Sabadell, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Pericay
authors.affiliation: Medical Oncology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Echavarria
authors.affiliation: Medical Oncology Department, Complejo Hospitalario de Navarra, Pamplona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Lacalle
authors.affiliation: Medical Oncology Department, Hospital Universitario Del Mar, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Visa
authors.affiliation: Pharmacy Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez Palomo
authors.affiliation: Medical Oncology Department, Hospital Galdakao-Usansolo, Galdakao-Usansolo, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Mangas
authors.affiliation: Medical Oncology Department, Hospital General de Ciudad Real, Ciudad Real, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Cano
authors.affiliation: Medical Oncology Department, Hospital Universitario Clinic, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Buxo
authors.affiliation: Pharmacy Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Álvarez-Manceñido
authors.affiliation: Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, IMIB, Avenida Marqués de los Vélez, 30008, Murcia, Spain.
authors.forename: T
authors.initials: T
authors.lastname: García
authors.affiliation: Medical Oncology Department, Hospital Universitario de Canarias, Tenerife, Spain.
authors.forename: J E
authors.initials: JE
authors.lastname: Lorenzo
authors.affiliation: Medical Oncology Department, Corporació Sanitària Parc Taulí , Sabadell, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ferrer-Cardona
authors.affiliation: Medical Oncology Department, Complejo Hospitalario de Navarra, Pamplona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Viudez
authors.affiliation: Medical Oncology Department, Hospital Universitario Son Espases, Mallorca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Azkarate
authors.affiliation: Medical Oncology Department, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ramchandani
authors.affiliation: Medical Oncology Department, Complejo Hospitalario de Orense, Orense, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Arias
authors.affiliation: Medical Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Longo
authors.affiliation: Medical Oncology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: C
authors.initials: C
authors.lastname: López
authors.affiliation: Medical Oncology Department, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Sánchez Bayona
authors.affiliation: Medical Oncology Department, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: M L
authors.initials: ML
authors.lastname: Limón
authors.affiliation: Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Díaz-Serrano
authors.affiliation: Medical Oncology Department, Complejo Hospitalario de Orense, Orense, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Fernández Montes
authors.affiliation: Medical Oncology Department, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Sala
authors.affiliation: Medical Oncology Department, Clínica Tecknon de Barcelona, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Cerdá
authors.affiliation: Medical Oncology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Rivera
authors.affiliation: Medical Oncology Department, Hospital General Universitario de Elche, Elche, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Gallego
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D012042:Registries; D013274:Stomach Neoplasms / Q000188:drug therapy*
chemical_list: D018943:Anthracyclines; D011743:Pyrimidines; D002945:Cisplatin
keywords: Anthracyclines; Epirubicin; Gastric cancer; Stomach; Triplets:doublets