title: Gemcitabine-erlotinib versus gemcitabine-erlotinib-capecitabine in the first-line treatment of patients with metastatic pancreatic cancer: Efficacy and safety results of a phase IIb randomised study from the Spanish TTD Collaborative Group.
abstract: Gemcitabine and erlotinib have shown a survival benefit in the first-line setting in metastatic pancreatic cancer (mPC). The aim of this study was to assess whether combining capecitabine (C) with gemcitabine + erlotinib (GE) was safe and effective versus GE in patients with mPC.
  
  
  
  Previously untreated mPC patients were randomised to receive G (1000 mg/m2, days 1, 8, 15) + E (100 mg/day, days 1-28) + C (1660 mg/m2, days 1-21) or GE, q4 weeks, until progression or unacceptable toxicity. Primary end-point: progression-free survival (PFS); secondary end-points: overall survival (OS), response rate, relationship of rash with PFS/OS and safety.
  
  
  
  120 patients were randomised, median age 63 years, ECOG status 0/1/2 33%/58%/8%; median follow-up 16.5 months. Median PFS in the gemcitabine-erlotinib-capecitabine (GEC) and GE arms was 4.3 and 3.8 months, respectively (hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.58-1.31; p = 0.52). Median OS in the GEC and GE arms was 6.8 and 7.7 months, respectively (HR: 1.09, 95% CI: 0.72-1.63; p = 0.69). Grade 3/4 neutropenia (GEC 43% versus GE 15%; p = 0.0008) and mucositis (GEC 9% versus GE 0%; p = 0.03) were the only statistically significant differences in grade 3/4 adverse events. PFS and OS were significantly longer in patients with rash (grade ≥1) versus no rash (grade = 0): PFS 5.5 versus 2.0 months (HR = 0.39, 95% CI: 0.26-0.6; p < 0.0001) and OS: 9.5 versus 4.0 months (HR = 0.51, 95% CI: 0.33-0.77; p = 0.0014).
  
  
  
  PFS with GEC was not significantly different to that with GE in patients with mPC. Skin rash strongly predicted erlotinib efficacy. The study was registered with ClinicalTrials.gov: NCT01303029.
authors.affiliation: Virgen de la Salud Hospital, Toledo, Spain. Electronic address: antonioirigoyen@yahoo.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Irigoyen
authors.affiliation: General Universitario de Elche Hospital, Alicante, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gallego
authors.affiliation: Universitario Ramón y Cajal Hospital, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Guillén Ponce
authors.affiliation: Navarra Hospital, Navarra, Spain.
authors.forename: Ruth
authors.initials: R
authors.lastname: Vera
authors.affiliation: General Hospital, Valencia, Spain.
authors.forename: Vega
authors.initials: V
authors.lastname: Iranzo
authors.affiliation: Hospital Regional Universitario y Virgen de la Victoria, Málaga, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ales
authors.affiliation: Donostia Hospital, Guipúzcoa, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Arévalo
authors.affiliation: Sabadell Hospital, Corporación Sanitaria Parc Tauli, Barcelona, Spain.
authors.forename: Aleydis
authors.initials: A
authors.lastname: Pisa
authors.affiliation: Santa Creu i Sant Pau Hospital, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Martín
authors.affiliation: Lleida Arnau de Vilanova Hospital, Lérida, Spain.
authors.forename: Antonieta
authors.initials: A
authors.lastname: Salud
authors.affiliation: Fundación Son Llatzer Hospital, Palma de Mallorca, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Falcó
authors.affiliation: Clínico Lozano Blesa Hospital, Zaragoza, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sáenz
authors.affiliation: Germans Trias i Pujol-ICO Hospital, Barcelona, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Manzano Mozo
authors.affiliation: Maimonides Institute of Biomedical Research (IMIBIC), Reina Sofía Hospital, University of Córdoba, Spanish Cancer Network (RTICC), Instituto de Salud Carlos III, Córdoba, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Pulido
authors.affiliation: Universitario Virgen de las Nieves Hospital, Granada, Spain.
authors.forename: Joaquina
authors.initials: J
authors.lastname: Martínez Galán
authors.affiliation: Aragon Institute of Biomedical Research (IISA), Miguel Servet University Hospital, Spanish Cancer Network (RTICC), Instituto de Salud Carlos III, Zaragoza, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pazo-Cid
authors.affiliation: Marqués de Valdecilla Hospital, Santander, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivera
authors.affiliation: Morales Meseguer Hospital, Murcia, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: García García
authors.affiliation: Moisés Broggi Hospital, Institut Català Oncologia - Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: Olbia
authors.initials: O
authors.lastname: Serra
authors.affiliation: Nuestra Señora de Valme Hospital, Sevilla, Spain.
authors.forename: Eva Ma
authors.initials: EM
authors.lastname: Fernández Parra
authors.affiliation: Fundación Hospital de Alcorcón, Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Hurtado
authors.affiliation: Puerta del Mar Hospital, Cádiz, Spain.
authors.forename: Ma José
authors.initials: MJ
authors.lastname: Gómez Reina
authors.affiliation: Virgen de la Salud Hospital, Toledo, Spain.
authors.forename: Luis Jesús
authors.initials: LJ
authors.lastname: López Gomez
authors.affiliation: Ciudad de Jaén Hospital, Jaén, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Martínez Ortega
authors.affiliation: Hospital Regional Universitario y Virgen de la Victoria, Málaga, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Benavides
authors.affiliation: Maimonides Institute of Biomedical Research (IMIBIC), Reina Sofía Hospital, University of Córdoba, Spanish Cancer Network (RTICC), Instituto de Salud Carlos III, Córdoba, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Aranda
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D013030:Spain / Q000453:epidemiology; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine
keywords: Capecitabine; Erlotinib; First-line; Gemcitabine; Metastatic pancreatic cancer