title: Italian multicenter phase III randomized study of cisplatin-etoposide with or without bevacizumab as first-line treatment in extensive stage small cell lung cancer: treatment rationale and protocol design of the GOIRC-AIFA FARM6PMFJM trial.
abstract: BACKGROUND
  Neoangiogenesis is particularly abundant in small-cell lung cancer (SCLC) and is associated with poor prognosis. As a result of the promising nature of phase II studies, a randomized phase III trial was designed to assess the efficacy of adding bevacizumab to first-line chemotherapy with cisplatin-etoposide for treatment of extensive disease SCLC. We present the treatment rationale and study design of GOIRC trial (FARM6PMFJM study), a multicenter randomized phase III study, supported by AIFA (Agenzia Italiana del Farmaco).
  
  
  METHODS
  Patients are randomized to receive either cisplatin 25 mg/m(2) and etoposide 100 mg/m(2) intravenously on days 1 to 3 (control arm) or the same chemotherapy combined with bevacizumab 7.5 mg/kg intravenously on day 1 (experimental arm). Treatment is repeated every 3 weeks and for a maximum of 6 courses. Patients randomized to the experimental arm in the absence of disease progression after 6 cycles continue bevacizumab alone until progression or for a maximum of 18 courses. Tumor assessment is done every 3 cycles. Major eligibility criteria are: age ≥ 18 years; histologically or cytologically documented extensive disease SCLC; Eastern Cooperative Oncology Group performance status ≤ 2; adequate hematological, hepatic and renal functions; no history of grade 2 or higher hemoptysis; and no evidence of tumor cavitation. The primary end point of this study is overall survival. Secondary end points include response rate, time to progression, and toxicity.
  
  
  CONCLUSIONS
  An interim futility analysis was performed by an Independent Data Monitoring Committee in September 2013 and the trial obtained approval to continue. As of July 31, 2014, 171 patients of 206 planned have been randomized.
authors.affiliation: Oncologia Medica, Azienda Ospedaliero-Universitaria, Parma, Italy. Electronic address: mtiseo@ao.pr.it.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tiseo
authors.affiliation: Clinical Trials Coordinating Center, Istituto Toscano Tumori, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Boni
authors.affiliation: Oncologia Medica, AORN Cardarelli, Napoli, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ambrosio
authors.affiliation: Oncologia Medica, Ospedale della Versilia, Lido di Camaiore, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Camerini
authors.affiliation: Oncologia Medica, AORN Cardarelli, Napoli, Italy.
authors.forename: Maria Giuseppa
authors.initials: MG
authors.lastname: Vitale
authors.affiliation: Oncologia Medica, Ospedale Campo di Marte, Lucca.
authors.forename: Editta
authors.initials: E
authors.lastname: Baldini
authors.affiliation: Oncologia Medica, Ospedale Perrino, Brindisi, Italy and IRCCS, Istituto Europeo di Oncologia, Milano, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinieri
authors.affiliation: IRCCS, Ospedale Santa Maria Nuova, Reggio Emilia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zanelli
authors.affiliation: Oncologia Medica, Ospedale Businco, Cagliari, Italy.
authors.forename: Efisio
authors.initials: E
authors.lastname: Defraia
authors.affiliation: Oncologia Medica, Ospedale Civile, Cremona, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Passalacqua
authors.affiliation: Oncologia Medica, Azienda Ospedaliero-Universitaria, Perugia, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Crino
authors.affiliation: Oncologia Medica, Ospedale Santa Maria delle Croci, Ravenna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Dazzi
authors.affiliation: Oncologia Medica, Ospedale Civile, Livorno, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Tibaldi
authors.affiliation: Oncologia Medica, Ospedale Civile Umberto I, Lugo di Romagna, Italy.
authors.forename: Gianni M
authors.initials: GM
authors.lastname: Turolla
authors.affiliation: Oncologia Medica, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: D'Alessandro
authors.affiliation: Oncologia Medica, Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Zilembo
authors.affiliation: Oncologia Medica, AORN Cardarelli, Napoli, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Riccardi
authors.affiliation: Oncologia Medica, Ospedale Sant'Orsola, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ardizzoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D002985:Clinical Protocols; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007558:Italy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012107:Research Design; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005047:Etoposide; D002945:Cisplatin
keywords: Bevacizumab; Extended disease; SCLC; Vascular endothelial growth factor