title: Cisplatin, Etoposide, and Bevacizumab Regimen Followed by Oral Etoposide and Bevacizumab Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer: A Single-Institution Experience.
abstract: Cisplatin and etoposide (PE) is the most used chemotherapy regimen in extensive-stage disease small-cell lung cancer (ED-SCLC), and usually achieves a high initial response rate. An intriguing maintenance strategy could be the combination of the angiogenic agent bevacizumab (Bev) with a convenient and well tolerated chemotherapy agent such as oral etoposide. Results of the current single-institutional phase II study suggest that a regimen that includes conventional PE chemotherapy combined with Bev followed by oral etoposide and Bev as maintenance treatment is feasible and effective in terms of 9-month disease control rate in patients with ED-SCLC.
  
  
  BACKGROUND
  In the present study we evaluated the efficacy and safety of a cisplatin (P), etoposide (E), and bevacizumab (Bev) regimen followed by maintenance oral E and Bev in patients with extensive-stage disease small-cell lung cancer (ED-SCLC).
  
  
  METHODS
  Patients were administered 3-day fractionated P 25 mg/m(2) and E 100 mg/m(2) on days 1 to 3, every 3 weeks. After 3 PE cycles, all patients whose disease did not progress continued treatment with PE combined with Bev 15 mg/kg on day 3 every 3 weeks. After completion of 3 PE/Bev cycles, patients who did not experience tumor progression continued maintenance treatment with oral E 50 mg on days 1 to 14 every 21 days combined with Bev 3 times per week until occurrence of disease progression or unacceptable toxicity.
  
  
  RESULTS
  At our institution, 22 patients were enrolled and their median age was 66 years (range, 38-79 years). After completion of induction chemotherapy (3 PE cycles with 3 PE/Bev cycles) the objective response rate was in 17 patients (77.2%) (95% confidence interval [CI], 54.6-92.1). Twenty-one patients received maintenance treatment with oral E and Bev. The 9-month disease control rate was 8 patients (36.3%). Median progression-free survival was 7.8 months (95% CI, 7.0-11.3 months) and median overall survival was 13.2 months (95% CI, 11.8-18.7 months). Grade 3 to 4 neutropenia occurred in 12 patients (54.4%) and 14 patients (63.6%) of patients during cycles 1 to 3 and cycles 4 to 6 of induction chemotherapy, respectively. Severe adverse events during maintenance treatment were rarely observed.
  
  
  CONCLUSIONS
  A PE and Bev regimen followed by oral E and Bev maintenance treatment appears feasible and effective in terms of 9-month disease control rate in patients with ED-SCLC.
authors.affiliation: Medical Oncology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy. Electronic address: r.petrioli@ao-siena.toscana.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Petrioli
authors.affiliation: Medical Oncology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Roviello
authors.affiliation: Medical Oncology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Laera
authors.affiliation: Unit of Thoracic Surgery, Surgery Department, University of Siena, Siena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Luzzi
authors.affiliation: Unit of Thoracic Surgery, Surgery Department, University of Siena, Siena, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Paladini
authors.affiliation: Unit of Thoracic Surgery, Surgery Department, University of Siena, Siena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ghiribelli
authors.affiliation: Unit of Thoracic Surgery, Policlinico Careggi, University of Firenze, Firenze, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Voltolini
authors.affiliation: Medical Oncology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Martellucci
authors.affiliation: Medical Oncology Unit, Policlinico Umberto I Hospital, University of Rome, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bianco
authors.affiliation: Medical Oncology Unit, Policlinico Umberto I Hospital, University of Rome, Rome, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Francini
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008175:Lung Neoplasms / Q000188:drug therapy*; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000068258:Bevacizumab; D005047:Etoposide; D019772:Topotecan; D002945:Cisplatin
keywords: Bevacizumab; Etoposide; Lung cancer; Maintenance; Small cell