Non-small cell lung cancer is a frequent type of cancer, with approximately 1.2 million cases per year expected worldwide. A total of 20-30% of patients with early stage non-small cell lung cancer are amenable to radical surgery, although only 40-50% of these patients are cured. An improvement in survival has never been demonstrated for postoperative radiotherapy. However, a major step forward is several recent large randomized studies that have demonstrated improved survival with postoperative chemotherapy. It is quite clear that adjuvant chemotehrapy benefits patients with stage II and III lung cancers. Post-operative adjuvant chemotherapy carries a small survival benefit in those patients with complete resection of their lung cancer. This survival benefit is in the region of a 4% absolute survival advantage at 5 years. Thus, 25 patients require chemotherapy to save one life at 5 years. The data is mixed for stage 1. Several guidelines adressed the issue of stage. I review the data briefly.
The UK National Institute for Health and Clinical Excellence (NICE) and the Scottish Intercollegiate Guidelines Network both issued guidelines on the management of lung cancer in February 2005 (www.nice.org.uk and www.sign.ac.uk). NICE concluded, ‘Adjuvant chemotherapy should be offered to NSCLC patients who have had a complete resection, with discussion of the risks and benefits’. However, NICE further described surgery and chemotherapy as ‘suitable for some patients’ in stage I, II and IIIA, although surgery alone remained ‘first choice for eligible patients’ in stage I and II.
Similarly, the SIGN guideline states ‘adjuvant chemotherapy should be considered for resected NSCLC, but discussed fully given the small margin of benefit, risks of toxicity and uncertainty as to which group of patients are likely to benefit’.
The NCCN Non-Small Cell Lung Cancer (NSCLC) guidelines panel recommended use of adjuvant chemotherapy in those who have undergone surgery for stages I, II, and IIIA NSCLC. The panel’s decision to include this recommendation was based on the presentation of survival data from the International Adjuvant Lung Cancer Trial (IALT) at the American Society of Clinical Oncology annual meeting in 2003, and the subsequent publication of the IALT study findings in the Jan. 22, 2004 issue of the New England Journal of Medicine.
The IALT study findings indicated a 4%-5% survival advantage for those who received cisplatin- (Platinol, Bristol-Myers Squibb) based adjuvant chemotherapy for all stages of the disease.
It should be evident that no single regimen can be recommended exclusive of others, since each positive study used a different combination. For this reason NCCN NSCLE-D, 2017 mentions all these regimens. NAVELBINE is indicated in combination with cisplatin for adjuvant chemo in stage III. Gemzar is indicated in combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer. It is not FDA approved for adjuvant therapy.
Patel MI and Wakelee HA (2011) Adjuvant chemotherapy for early stage non-small cell lung cancer. Front. Oncol. 1:45.
nccn.org, nonsmall cell lung cancer 2012
Le Chevalier T. Adjuvant chemotherapy for resectable non-small-cell lung cancer: where is it going? Ann Oncol. 2010 Oct;21 Suppl 7:vii196-8.
Arriagada R, Bergman B, Dunant A et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected nonsmall- cell lung cancer. N Engl J Med. 2004; 350:351-60.
Scagliotti GV, Fossati R, Torri V et al. Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small cell lung cancer. J Natl Cancer Inst. 2003; 95:1453-61.
Kato H, Ichinose Y, Ohta M et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med. 2004; 350: 1713-21.
Hotta K, Matsuo K, Ueoka H et al. Role of adjuvant chemotherapy in patients with resected non-small-cell lung cancer: reappraisal with a meta-analysis of randomized controlled trials. J Clin Oncol. 2004; 22:3860-7.
Winton TL, Livingston R, Johnson D et al., for the National Cancer Institute of Canada Clinical Trials Group. A prospective randomised trial of adjuvant vinorelbine (VIN) and cisplatin (CIS) in completely resected stage 1B and II non small cell lung cancer (NSCLC) intergroup JBR. J Clin Oncol. 2004; 22:A7018.
Strauss GM, Herndon J, Maddaus MA et al. Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell lung cancer (NSCLC): report of cancer and leukemia group B (CALGB) protocol 9633. J Clin Oncol. 2004; 22:A7019.
Robinson LA, Wagner H Jr, Ruckdeschel JC. Treatment of stage IIIA non-small cell lung cancer. Chest 2003 Jan;123(1 Suppl):202S-20S. [109 references)
Douillard J, Rosell R, Delena M, Legroumellec A, Torres A, Carpagnano F. ANITA: phase III adjuvant vinorelbine and cisplatin versus observation in completely resected (stage I-III) non-small cell lung cancer patients: final results after 70-month median follow-up. J Clin Oncol 2005; 23 Suppl 16S: 624s.
Keller SM, Adak S, Wagner H, Herskovic A, Komaki R, Brooks BJ, Perry MC, Livingston RB, Johnson DH, for the Eastern Cooperative Oncology Group. A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer. N Engl J Med 2000; 343: 1217-1222.
Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ 1995; 311: 899-909.
Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, Le Chevalier T. Lung Adjuvant Cisplatin Evaluation (LACE): A pooled analysis of five randomized clinical trials including 4,584 patients. Proc Am Soc Clin Oncol 2006 Part I: abstr 7008.
Charlotte LoBuono. Lung cancer guidelines revised to include latest drugs. Drug Topics Apr. 5, 2004;148:32.
Scagliotti GV, Fossati R, Torri V, Crino L, Giaccone G, Silvano G, Martelli M, Clerici M, Cognetti F, Tonato M. Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small-cell lung cancer. J Natl Cancer Inst 2003; 95: 1453-1461.
Strauss GM, Herndon J, Maddaus MA, Johnstone DW, Johnson EA, Watson DM, Sugarbaker DJ, Schilsky RL, Green MR. Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in Stage IB non-small cell lung cancer (NSCLC): Report of Cancer and Leukemia Group B (CALGB) Protocol 9633. Proc Am Soc Clin Oncol 2004; abstr 7019.
Strauss GM, Herndon JE, Maddaus MA, Johnstone DW, Johnson EA, Watson DM, Sugarbaker DJ, Schilsky RA, Vokes EE, Green MR. Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): Update of Cancer and Leukemia Group B (CALGB) protocol 9633. Proc Am Soc Clin Oncol 2006 Part I: abstr 7007.
The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med 2004; 350: 351-360.
Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, Fry W, Bethune D, Ayoub J, Ding K, Seymour L, Graham B, Tsao M, Gandara D, Kesler K, Demmy T, Shepherd F. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005; 352: 2589-2597.
Vansteenkiste JF, Schildermans RH. The future of adjuvant chemotherapy for resected non-small cell lung Expert Rev Anticancer Ther. 2005 Feb;5(1):165-75.cancer.