title: Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy.
abstract: OBJECTIVE
  To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy.
  
  
  METHODS
  Randomized, multicenter, phase III study, 551 patients received either vinflunine 320 mg/m(2) or docetaxel 75 mg/m(2) every 21 days until disease progression or serious toxicity. The primary end point was progression-free survival (PFS). The noninferiority analysis was based on a 10% difference (types I/II error rates: 5%/20%). Secondary end points included response rate (ORR), response duration, overall survival (OS), clinical benefit, quality of life (QOL), and safety.
  
  
  RESULTS
  Median PFS was 2.3 months for each arm (HR, 1.004; 95% CI, 0.841 to 1.199). ORR, stable disease, median OS, were 4.4% versus 5.5%, 36.0% versus 39.6%, 6.7 versus 7.2 months (HR, 0.973; 95% CI, 0.805 to 1.176), respectively. No significant difference in patient benefit and QOL (Functional Assessment of Cancer Therapy-Lung). No unexpected adverse events were observed. Grade higher than 0 (vinflunine v docetaxel) anemia (82.1% v 79.8%), neutropenia (49.3 v 39.02%), thrombocytopenia (30.6% v 14.3%), febrile neutropenia (3.3% v 4.7%), constipation (39.2% v 11.7%), fatigue (36.6% v 33.9%), injection site reaction (31.9% v 0.7%), nausea (26.7% v 23.7%), vomiting (23.8% v 14.2%), alopecia (19.8% v 35.4%), stomatis (19.4% v 12.4%), abdominal pain (20.1% v 3.6%), myalgia (14.7% v 6.6%), peripheral neuropathy (10.7% v 15.0%), arthralgia (7.0% v 7.7%), diarrhea (6.2% v 12.4%), edema (1.5% v 5.4%), and nail disorders (1.1% v 5;1%) were observed.
  
  
  CONCLUSIONS
  This noninferiority phase III study showed similar efficacy end points for vinflunine and docetaxel. Despite higher rates of some adverse effects (anemia, abdominal pain, constipation, fatigue) the overall toxicity profile of vinflunine was manageable. Therefore, VFL may be another option in the second-line treatment of patients with advanced NSCLC.
authors.affiliation: Centrum Onkologii Instytut, Warsaw, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Krzakowski
authors.forename: Rodryg
authors.initials: R
authors.lastname: Ramlau
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szczesna
authors.forename: Petr
authors.initials: P
authors.lastname: Zatloukal
authors.forename: Joachim
authors.initials: J
authors.lastname: Von Pawel
authors.forename: Xushan
authors.initials: X
authors.lastname: Sun
authors.forename: Jaafar
authors.initials: J
authors.lastname: Bennouna
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.forename: Bonne
authors.initials: B
authors.lastname: Biesma
authors.forename: François M
authors.initials: FM
authors.lastname: Delgado
authors.forename: Yacine
authors.initials: Y
authors.lastname: Salhi
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vaissiere
authors.forename: Olfred
authors.initials: O
authors.lastname: Hansen
authors.forename: Eng-Huat
authors.initials: EH
authors.lastname: Tan
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Quoix
authors.forename: Pilar
authors.initials: P
authors.lastname: Garrido
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D000077143:Docetaxel; D005060:Europe; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017671:Platinum Compounds / Q000008:administration & dosage; D011788:Quality of Life; D012846:Singapore; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D017671:Platinum Compounds; D043823:Taxoids; D000077143:Docetaxel; C111217:vinflunine; D014747:Vinblastine