Preoperative chemotherapy in patients with resectable non-small cell lung cancer : results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review

Gilligan, David; Nicolson, Marianne; Smith, Ian; van Meerbeeck, Jan; et al.

doi:10.1016/S0140-6736(07)60714-4

Title

Preoperative chemotherapy in patients with resectable non-small cell lung cancer : results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review

Author

Gilligan, David

Nicolson, Marianne

Smith, Ian

van Meerbeeck, Jan

et al.

Abstract

Background Although surgery offers the best chance of cure for patients with non-small cell lung cancer (NSCLC), the overall 5-year survival rate is modest, and improvements are urgently needed. In the 1990s, much interest was generated from two small trials that reported striking results with neo-adjuvant chemotherapy, and therefore our intergroup randomised trial was designed to investigate whether, in patients with operable non-small cell lung cancer of any stage, outcomes could be improved by giving platinum-based chemotherapy before surgery. Methods Patients were randomised to receive either surgery alone (S), or three cycles of platinum-based chemotherapy followed by surgery (CT-S). Before randomisation, clinicians chose the chemotherapy that would be given from a list of six standard regimens. The primary outcome measure was overall survival, which was analysed on an intention-to-treat basis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN25582437. Results 519 patients were randomised (S: 261, CT-S: 258) from 70 centres in the UK, Netherlands, Germany, and Belgium. Most (61%) were clinical stage I, with 31% stage II, and 7% stage III. Neo-adjuvant chemotherapy was feasible (75% of patients received all three cycles of chemotherapy), resulted in a good response rate (49% [95% CI 43%-55%]) and down-staging in 31% (25%-37%) of patients, and did not alter the type or completeness of the surgery (lobectomy: S: 56%, CT-S: 60%, complete resection: S: 80%, CT-S: 82%). Post-operative complications were not increased in the CT-S group, and no impairment of quality of life was observed. However, there was no evidence of a benefit in terms of overall survival (hazard ratio [HR] 1.02, 95% Cl 0.80-1.31, p=0.86). Updating the systematic review by addition of the present result suggests a 12% relative survival benefit with the addition of neoadjuvant chemotherapy (1507 patients, HR 0.88, 95% CI 0.76-1.01, p=0.07), equivalent to an absolute improvement in survival of 5% at 5 years Interpretation Although there was no evidence of a difference in overall survival with neo-adjuvant chemotherapy, the result is statistically consistent with previous trials, and therefore adds considerable weight to the current evidence.

Language

English

Source (journal)

The lancet : international edition. - London, 1823, currens

Publication

London : 2007

ISSN

0140-6736 [print]

1474-547X [online]

DOI

10.1016/S0140-6736(07)60714-4

Volume/pages