Cell cycle regulators and outcome of adjuvant cisplatin-based chemotherapy in completely resected non-small-cell lung cancer: the International Adjuvant Lung Cancer Trial Biologic Program

J Clin Oncol. 2007 Jul 1;25(19):2735-40. doi: 10.1200/JCO.2006.08.2867.


Purpose: The International Adjuvant Lung Cancer Trial (IALT) demonstrated that adjuvant cisplatin-based chemotherapy improves the survival of patients with completely resected non-small-cell lung cancer (NSCLC). The purpose of our study was to determine whether cell cycle regulators are of prognostic and/or predictive value in patients who were enrolled onto the IALT.

Patients and methods: Expression of p27Kip1, p16INK4A, cyclin D1, cyclin D3, cyclin E, and Ki-67 was immunohistochemically assessed in tumor specimens obtained from 778 IALT patients. Prognostic and predictive analyses were based on Cox models adjusted for clinical and pathologic parameters.

Results: There was a relationship between p27Kip1 status and benefit of cisplatin-based chemotherapy (test for interaction, P = .02). Among patients with p27Kip1-negative tumors, cisplatin-based chemotherapy resulted in longer overall survival compared with controls (adjusted hazard ratio [HR] for death = 0.66; 95% CI, 0.50 to 0.88; P = .006). In patients with p27Kip1-positive tumors, overall survival was not different between patients treated with cisplatin-based chemotherapy and controls (adjusted HR for death = 1.09; 95% CI, 0.82 to 1.45; P = .54). The other cell cycle regulators and Ki-67 did not predict benefit of adjuvant cisplatin-based chemotherapy. None of these biomarkers was significantly associated with overall survival of the patients in the total study population.

Conclusion: NSCLC patients with p27Kip1-negative tumors benefit from adjuvant cisplatin-based chemotherapy after complete tumor resection. Before establishing p27Kip1 as a routine marker for selection of patients for adjuvant chemotherapy, the predictive value of p27Kip1 has to be confirmed in patients from other trials.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / surgery*
  • Cell Cycle*
  • Chemotherapy, Adjuvant*
  • Cisplatin / therapeutic use*
  • Cyclin-Dependent Kinase Inhibitor p27
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / surgery*
  • Male
  • Middle Aged
  • Prognosis
  • Treatment Outcome


  • Antineoplastic Agents
  • CDKN1B protein, human
  • Intracellular Signaling Peptides and Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cisplatin