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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.

Abstract : 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.
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https://www.hal.inserm.fr/inserm-00372214
Contributor : Sylvie Lantuejoul <>
Submitted on : Tuesday, March 31, 2009 - 3:31:38 PM
Last modification on : Thursday, August 27, 2020 - 11:36:03 AM

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Martin Filipits, Robert Pirker, Ariane Dunant, Sylvie Lantuejoul, Katharina Schmid, et al.. 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.. Journal of Clinical Oncology, American Society of Clinical Oncology, 2007, 25 (19), pp.2735-40. ⟨10.1200/JCO.2006.08.2867⟩. ⟨inserm-00372214⟩

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