title: Oral vinorelbine plus cisplatin as first-line chemotherapy in nonsquamous non-small-cell lung cancer: final results of an International randomized phase II study (NAVotrial 01).
abstract: BACKGROUND
  The combination of oral vinorelbine plus cisplatin has been studied in numerous trials as first-line treatment of patients with non-small cell lung cancer (NSCLC) regardless of histologic subtype. NAVoTrial 01 is the first study that explores this combination specifically in nonsquamous (NS) NSCLC by assessing the feasibility of this doublet (ratio 1:2) in an investigational approach. A reference arm with pemetrexed plus cisplatin was included. Maintenance therapy with single-agent therapy after 4 cycles of combination therapy was included in the study schedules because it reflected a trend in first-line treatment of NSCLC.
  
  
  METHODS
  Stage IIIB/IV untreated/relapsed patients with NS NSCLC received a 3-week cycle of pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) on day 1 (arm A) or oral vinorelbine 80 mg/m(2) on days 1 and 8 (first cycle 60 mg/m(2)) and cisplatin 80 mg/m(2) on day 1 (arm B). After 4 cycles, patients without disease progression received single-agent maintenance treatment with pemetrexed or oral vinorelbine.
  
  
  RESULTS
  Overall, 153 patients were randomized (arm A/arm B: 51/102). Disease control rate (%) for arm A was 76.5 (95% confidence interval [CI], 62.5-87.2) and for arm B it was 75.0 (95% CI, 65.3-83.1), Response rates for arm A were 31.4% (95% CI, 19.1-45.9) and for arm B were 24.0% (95% CI, 16.0-33.6). Median progression-free survival for arm A was 4.3 months (95% CI, 3.8-5.6) and for arm B it was 4.2 months (95% CI, 3.6-4.7). Median survival for arm A was 10.8 months (95% CI, 7.0-16.4) and for arm B it was 10.2 months (95% CI, 7.8-11.9). Main grade 3/4 hematologic toxicities were neutropenia 18.3% (arm A) and 44.0% (arm B), whereas febrile neutropenia was reported in 2% of patients in each arm.
  
  
  CONCLUSIONS
  Oral vinorelbine and cisplatin had an efficacy in line with that achieved with a standard treatment such as pemetrexed and cisplatin, coupled with an acceptable safety profile.
authors: Institut de Cancérologie de l'Ouest, Nantes, France.
authors: Jaafar
authors: J
authors: Bennouna
authors: Department of Pneumology and Thoracic Surgery, University Hospital Bulovka, Prague, Czech Republic.
authors: Libor
authors: L
authors: Havel
authors: Maria Sklodowska-Curie Oncology Centre, Institute of Oncology, Chest Oncology, Warsaw, Poland.
authors: Maciej
authors: M
authors: Krzakowski
authors: Department of Pneumology, Lungenklinik Heckeshorn, Helios-Klinikum Emil von Behring, Berlin, Germany.
authors: Jens
authors: J
authors: Kollmeier
authors: Department of Oncology, Centre François Baclesse, Caen, France.
authors: Radj
authors: R
authors: Gervais
authors: Department of Oncology, Centre Oscar Lambret, Lille, France.
authors: Eric
authors: E
authors: Dansin
authors: Department of Pneumology III, Lungenklinik Hemer, Hemer, Germany.
authors: Monika
authors: M
authors: Serke
authors: Veneto Institute of Oncology IOV-IRCCS, Second Medical Oncology Unit, Padova, Italy.
authors: Adolfo
authors: A
authors: Favaretto
authors: Department of Oncology, Mazowieckie Centrum ChorobPluciGruzlicy, Otwocku, Poland.
authors: Aleksandra
authors: A
authors: Szczesna
authors: Department of Medical Oncology, Hospital Clinico Carlos Haya, Malaga, Spain.
authors: Manuel
authors: M
authors: Cobo
authors: Ospedale Molinette, Oncologia Medica, Torino, Italy.
authors: Libero
authors: L
authors: Ciuffreda
authors: Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland.
authors: Jacek
authors: J
authors: Jassem
authors: Ospedale Cervesi, U.O.S. di Oncologia, Cattolica, Italy.
authors: Mario
authors: M
authors: Nicolini
authors: Department of Oncology, Wielkopolskie Centrum Pulmonologii Torakochirurgii, Poznan, Poland.
authors: Rodryg
authors: R
authors: Ramlau
authors: Ospedale Versilia, UOC Oncologia Medica, Lido di Camaiore, Italy.
authors: Domenico
authors: D
authors: Amoroso
authors: Department of Medical Oncology, S Orsola-Malpighi Hospital, Bologna, Italy.
authors: Barbara
authors: B
authors: Melotti
authors: Department of Oncology, Instituto Portugues De Oncologia, Porto, Portugal.
authors: Teresa
authors: T
authors: Almodovar
authors: Department of Oncology, Institut de Recherche Pierre Fabre, Paris, France. Electronic address: marcello.riggi@pierre-fabre.com.
authors: Marcello
authors: M
authors: Riggi
authors: Department of Oncology, Institut de Recherche Pierre Fabre, Paris, France.
authors: Noël-Raphaël
authors: NR
authors: Caux
authors: Department of Oncology, Institut de Recherche Pierre Fabre, Paris, France.
authors: Nathalie
authors: N
authors: Vaissière
authors: Department of Medical Oncology, National Cancer Centre, Singapore.
authors: Eng-Huat
authors: EH
authors: Tan
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007391:International Cooperation; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D000068437:Pemetrexed; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D014747:Vinblastine; D006147:Guanine; D002945:Cisplatin; D000077235:Vinorelbine
keywords: Advanced non–small-cell lung cancer; Chemotherapy; Nonsquamous histologic subtype; Pemetrexed; Vinorelbine