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

2.50
Hdl Handle:
http://hdl.handle.net/10541/70175
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
Authors:
Gilligan, David; Nicolson, Marianne; Smith, Ian; Groen, Harry; Dalesio, Otilia; Goldstraw, Peter; Hatton, Matthew; Hopwood, Penelope; Manegold, Christian; Schramel, Franz; Smit, Hans; Van Meerbeeck, Jan; Nankivell, Matthew; Parmar, Mahesh K B; Pugh, Cheryl; Stephens, Richard J
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% CI 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.
Affiliation:
Addenbrooke's Hospital, Cambridge, UK.
Citation:
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. 2007, 369 (9577):1929-37 Lancet
Journal:
Lancet
Issue Date:
9-Jun-2007
URI:
http://hdl.handle.net/10541/70175
DOI:
10.1016/S0140-6736(07)60714-4
PubMed ID:
17544497
Type:
Article
Language:
en
ISSN:
1474-547X
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorGilligan, David-
dc.contributor.authorNicolson, Marianne-
dc.contributor.authorSmith, Ian-
dc.contributor.authorGroen, Harry-
dc.contributor.authorDalesio, Otilia-
dc.contributor.authorGoldstraw, Peter-
dc.contributor.authorHatton, Matthew-
dc.contributor.authorHopwood, Penelope-
dc.contributor.authorManegold, Christian-
dc.contributor.authorSchramel, Franz-
dc.contributor.authorSmit, Hans-
dc.contributor.authorVan Meerbeeck, Jan-
dc.contributor.authorNankivell, Matthew-
dc.contributor.authorParmar, Mahesh K B-
dc.contributor.authorPugh, Cheryl-
dc.contributor.authorStephens, Richard J-
dc.date.accessioned2009-06-11T11:05:05Z-
dc.date.available2009-06-11T11:05:05Z-
dc.date.issued2007-06-09-
dc.identifier.citationPreoperative 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. 2007, 369 (9577):1929-37 Lanceten
dc.identifier.issn1474-547X-
dc.identifier.pmid17544497-
dc.identifier.doi10.1016/S0140-6736(07)60714-4-
dc.identifier.urihttp://hdl.handle.net/10541/70175-
dc.description.abstractBACKGROUND: 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% CI 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.en
dc.language.isoenen
dc.subjectLung Canceren
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshCarcinoma, Non-Small-Cell Lung-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshLung Neoplasms-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshPreoperative Care-
dc.subject.meshQuality of Life-
dc.subject.meshQuestionnaires-
dc.subject.meshSurvival Analysis-
dc.titlePreoperative 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 reviewen
dc.typeArticleen
dc.contributor.departmentAddenbrooke's Hospital, Cambridge, UK.en
dc.identifier.journalLanceten

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