title: Cisplatin-based three drugs combination (NIP) as induction and adjuvant treatment in locally advanced non-small cell lung cancer: final results.
abstract: BACKGROUND
  This phase III trial was conducted in non-small cell lung cancer patients with locally advanced stage II B (only T3N0) III A and III B (only T4 N0). Primary endpoint was 2-year survival; secondary were toxicity, disease-free survival, and overall survival.
  
  
  METHODS
  After three cycles of vinorelbine (N) 25 mg/m2 on days 1 and 5, ifosfamide/mesna (I) 3 g/m2 on day 1, cisplatin (P) (NIP), patients were treated by surgery and within 45 days were randomized to two additional cycles of NIP versus observation.
  
  
  RESULTS
  Median tumor diameter was 5.5 cm (1.2-10.6). Overall, 155 of 156 patients received chemotherapy: 133 (85%) men, median age: 59 years (35-75). Sixty-five percentage of patients were stage III A, 28% II B, and 7% III B. The study has been closed prematurely because of the low inclusion rate. After three cycles of induction in 143 assessable patients, 82 reported an objective response (57.3%) (95% CI: 48.8-65.6), with 3.5% complete response and 53.8% partial response. Relative dose intensity during neoadjuvant NIP (%) was 97, 98, and 98.5 for vinorelbine, ifosfamide/mesna, and cisplatin, respectively. Tolerance: G3 to 4 neutropenia in 3% of patients and G3 to 4 anemia in 4%; nonhematological toxicities included G3 nausea/vomiting in 11%, G3 anorexia and G3 to 4 infection in 6.5%, G3 asthenia in 10% and G3 to 4 alopecia in 25.5%. After a median of 32 days after NIP, 107 patients (69%) underwent operation with complete resection (R0) in 74% (79 of 107 patients). Downstaging (N2 to N0) after surgery was 29%. Operative mortality rate was 2.8%. Twenty-one days (median) after surgery, 79 patients were randomized to adjuvant NIP (47%) or control (53%). Tolerance of adjuvant NIP: 12.5% G3 to 4 nausea/vomiting, 19% G3 alopecia, 6% G3 infection, and G3 asthenia. Overall median survival 32.3 versus 31.8 months in the observation and NIP arms, respectively.
  
  
  CONCLUSIONS
  NIP allows 74% of R0 with no surgery delay. The few number of randomized patients did not allow to conclude on the efficacy of adjuvant chemotherapy.
authors.affiliation: Meir Medical Center, Kfar-Saba, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Gottfried
authors.forename: Rodryg
authors.initials: R
authors.lastname: Ramlau
authors.forename: Maciej
authors.initials: M
authors.lastname: Krzakowski
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Ziolo
authors.forename: Henryk
authors.initials: H
authors.lastname: Olechnowicz
authors.forename: Leona
authors.initials: L
authors.lastname: Koubkova
authors.forename: Jubrail
authors.initials: J
authors.lastname: Dahabreh
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szczesna
authors.forename: Guillermo Lopez
authors.initials: GL
authors.lastname: Vivanco
authors.forename: Reury-Perng
authors.initials: RP
authors.lastname: Perng
authors.forename: Francesco
authors.initials: F
authors.lastname: Carpagnano
authors.forename: Swan-Swan
authors.initials: SS
authors.lastname: Leong
authors.forename: Alberto
authors.initials: A
authors.lastname: Fittipaldo
authors.forename: Cecilia
authors.initials: C
authors.lastname: De Almeida
authors.forename: Delphine
authors.initials: D
authors.lastname: Aubert
authors.forename: Dominique
authors.initials: D
authors.lastname: Grunenwald
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D007069:Ifosfamide