A Prospective Randomized Study of Adjuvant Chemotherapy with Navelbine + Cisplatin in Completely Resected Non-Small Cell Lung  (the ANITA trial)

Reviewer: S. Jack Wei, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 16, 2005

Presenter: J.Y. Douillard
Presenter's Affiliation: Adjuvant Navelbine International Trialist Association
Type of Session: Scientific


  • Recent randomized trials have shown an overall survival (OS) benefit to adjuvant chemotherapy added to definitive surgery for stage I-III NSCLC.
  • However, there is still question regarding the exact stages of patients that benefit from this treatment and the type of chemotherapy that should be used.

Materials and Methods

  • Stage IB-IIIA patients with NSCLC who underwent definitive surgical resection were randomized to:
    1. Observation
    2. Navelbine (NVB) (30 mg/m2 IV qwk) x 16/20 + cisplatin (CDDP) (100 mg/m2 IV d1,d29,d57,d85)
  • Patients were included if they had histologically proven NSCLC who underwent total surgical resection within 42 days of trial enrollment, WHO performance status (PS) 0-2, Age >18 and <=75, and fit to receive chemotherapy.
  • Patients were stratified by treating center, stage, and histology.
  • Primary objective is overall survival with secondary endpoints of relapse free survival and chemotherapy-related toxicity.


  • Between 12/94 and 12/00, a total of 840 patients were enrolled (433 observation, 407 NVB+CDDP)
  • 2 patients on the observation arm received chemotherapy and 39 patients on the NVB+CDDP arm did not receive any chemotherapy.
  • Patient arms were well balanced for age, gender, performance status, type of surgery received, stage, and histology.
  • For patients receiving chemotherapy, the median relative dose intensity (RDI) of NVB was 58.6% and the median RDI of CDDP was 88.9%.
  • Chemotherapy related toxicity included hematologic, febrile neutropenia, infection, anorexia, nausea/vomitting, asthenia, and neuropathy including treatment-related deaths in 1.7% of patients.
  • Median follow was >70 months.
  • Median relapse-free survival = Obs 20.7 mo vs. NVB+CDDP 36.3 mo (p=0.002)
  • Median OS = Obs 43.8 mo vs. 65.8 mo (p=0.013)
  • 2-yr survival = 62.8% vs. 67.9% (p=0.013)
  • 5-yr survival = 42.6% vs. 51.2%
  • 7-yr survival = 36.8% vs. 45.2%
  • Median survival for stage I patients = Obs 99.7 mo vs. NVB + CDDP Not Yet Reached (p=NS)
  • Median survival for stage II patients = Obs 36.5 mo vs. NVB + CDDP 65.8 mo
  • Median survival for stage III patients = Obs 24.1 mo vs. NVB + CDDP 38.6 mo

Author's Conclusions

  • Adjuvant NVB + CDDP significantly improves RFS and long-term OS in patients with completely resected NSCLC.
  • NVB + CDDP is feasable and safe adjuvant treatment.
  • Early stage (IB) NSCLC does not seem to benefit from NVB + CDDP chemotherapy.
  • NVB + CDDP should be considered as standard of care for stage II and IIIA NSCLC.

Clinical/Scientific Implications

This trial adds to the growing evidence that adjuvant chemotherapy after definitive surgical resection for NSCLC improves overall survival.  There did not appear to be a benefit for stage IB patients which is in direct contrast to the JBR10 study presented at ASCO last year.  In that study, only stage IB patients were included and a 5-year overall survival advantage of 12% was seen with the addition of carboplatin/paclitaxel chemotherapy after surgery.  In addition, the CALGB study which was also presented last year resulted in an increased 4-year OS of 14% in stage IB and II NSCLC patients.  It is unclear why this difference exists; however, it should be kept in mind that the lack of benefit seen in this trial was only seen on subset analysis.  As it stands, adjuvant chemotherapy should remain the standard for completely resected patients with stage II and IIIA patients.  For stage IB patients, adjuvant chemotherapy should be offered to eligible patients.  The exact chemotherapy agents to use is still unclear; however, given the results of all the adjuvant chemotherapy trials thus far carboplatin/paclitaxel or a cisplatinum-containing doublet appear to be reasonable options.

Frequently Asked Questions