What is the role of chemotherapy before surgery in the treatment of operable stage I NSCLC?

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What is the role of chemotherapy before surgery in the treatment of operable stage I NSCLC?

Pre-operative neoadjuvant chemotherapy for stage IA

The pre-operative adjuvant therapy approach is predicated on clinical staging, which is principally based on radiological findings, rather than histological evaluation (aside from diagnostic biopsies). The majority of studies evaluating neoadjuvant (or pre-operative) chemotherapy for early stage NSCLC either excluded patients with clinical stage IA disease, or if included they represented a small percentage of the patients. Most studies do not segregate the stage I categories, and often pool stage I and II together in the study analyses. This makes subgroup evaluation of stage IA difficult or impossible. In studies where stage IA disease has been evaluated as a separate subgroup, the results have been variable. There is no confirmed survival benefit.

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Pre-operative neoadjuvant chemotherapy for stage IB

The benefit of chemotherapy before surgery is not well established in stage IB NSCLC. The French Thoracic Cooperative Group performed a trial of neoadjuvant cisplatin based chemotherapy in operable stage I,II and III NSCLC. A survival benefit was demonstrated in the pooled stage I and II subgroup.[1] One hundred and thirty one (131) of the total of 355 patients in this study had stage I disease. The Big Lung Trial (BLT/LU22) did not demonstrate a survival benefit for neoadjuvant chemotherapy in the overall study population, which included stage I, II and III NSCLC.[2] An associated systematic review did reveal a benefit.[3] A meta-analysis of 13 randomised controlled trials also showed a benefit, but this was particularly evident for patients with stage III NSCLC, whilst the findings for stage I and II were inconclusive.[4] A previous systematic review produced similar conclusions.[5] The Spanish Lung Cancer Group conducted a trial comparing surgery alone to neoadjuvant chemotherapy or post-operative chemotherapy (Carboplatin + Paclitaxel x three cycles). No benefit was seen with chemotherapy in stage I patients, regardless of whether the chemotherapy was administered before or after the surgery.[6] A meta-analysis comparing post-operative and pre-operative chemotherapy did not find a difference in outcome according to the timing of the chemotherapy around surgery.[7]

Brouchet et al[8] reported that pre-operative chemotherapy did not increase post-operative complications. In a phase II study from Japan, there were more complications post surgery if neoadjuvant chemotherapy is combined with radiotherapy and the dose of radiotherapy was greater than 45Gy.[9]

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Evidence summary and recommendations

Evidence summary Level References
There is insufficient data to support the use of chemotherapy before surgery for stage IA NSCLC.

Last reviewed December 2015

I, II [7], [6], [1]
Evidence-based recommendationQuestion mark transparent.png Grade
Neoadjuvant chemotherapy is not considered standard therapy for stage IA NSCLC.

Last reviewed December 2015

B


Evidence summary Level References
There is insufficient data to support the administration of chemotherapy before surgery for stage IB NSCLC.

Last reviewed December 2015

I, II [7], [6], [1]
Evidence-based recommendationQuestion mark transparent.png Grade
Neoadjuvant chemotherapy is not considered standard therapy for stage IB NSCLC.

Last reviewed December 2015

B


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References

  1. 1.0 1.1 1.2 Depierre A, Milleron B, Moro-Sibilot D, Chevret S, Quoix E, Lebeau B, et al. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol 2002 Jan 1;20(1):247-53 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11773176.
  2. Waller D, Peake MD, Stephens RJ, Gower NH, Milroy R, Parmar MK, et al. Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial. Eur J Cardiothorac Surg 2004 Jul;26(1):173-82 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15200998.
  3. Gilligan D, Nicolson M, Smith I, Groen H, Dalesio O, Goldstraw P, et al. 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. Lancet 2007 Jun 9;369(9577):1929-37 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17544497.
  4. Song WA, Zhou NK, Wang W, Chu XY, Liang CY, Tian XD, et al. Survival benefit of neoadjuvant chemotherapy in non-small cell lung cancer: an updated meta-analysis of 13 randomized control trials. J Thorac Oncol 2010 Apr;5(4):510-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20107424.
  5. Burdett S, Stewart LA, Rydzewska L. A systematic review and meta-analysis of the literature: chemotherapy and surgery versus surgery alone in non-small cell lung cancer. J Thorac Oncol 2006 Sep;1(7):611-21 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17409927.
  6. 6.0 6.1 6.2 Felip E, Rosell R, Maestre JA, Rodríguez-Paniagua JM, Morán T, Astudillo J, et al. Preoperative chemotherapy plus surgery versus surgery plus adjuvant chemotherapy versus surgery alone in early-stage non-small-cell lung cancer. J Clin Oncol 2010 Jul 1;28(19):3138-45 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20516435.
  7. 7.0 7.1 7.2 Lim E, Harris G, Patel A, Adachi I, Edmonds L, Song F. Preoperative versus postoperative chemotherapy in patients with resectable non-small cell lung cancer: systematic review and indirect comparison meta-analysis of randomized trials. J Thorac Oncol 2009 Nov;4(11):1380-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19861907.
  8. Brouchet L, Bauvin E, Marcheix B, Bigay-Game L, Renaud C, Berjaud J, et al. Impact of induction treatment on postoperative complications in the treatment of non-small cell lung cancer. J Thorac Oncol 2007 Jul;2(7):626-31 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17607118.
  9. Fujita S, Katakami N, Takahashi Y, Hirokawa K, Ikeda A, Tabata C, et al. Postoperative complications after induction chemoradiotherapy in patients with non-small-cell lung cancer. Eur J Cardiothorac Surg 2006 Jun;29(6):896-901 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16675259.

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Appendices

Further resources

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