Treatment Therapies
Chemotherapy
Adjuvant and Neoadjuvant
The use of chemotherapy as an adjunct to surgery for the treatment of resectable early-stage NSCLC is now understood to provide significantly improved survival rates.1,2 An early meta-analysis of more than 4,000 patients included in clinical trials, which compared surgery only with surgery plus chemotherapy, described a 5% survival benefit at 5 years for conventional cisplatin-based treatments.3 This analysis is supported by a recent, large-scale (1,867 patients) adjuvant trial that showed a 4% survival benefit at 5 years4 and the positive trial results presented at ASCO 2004.5,6
There is some evidence from randomised trials, which enrolled patients with resectable stage III disease, that neoadjuvant chemotherapy (chemotherapy before surgery) is better than surgery alone.7,8 This approach remains investigational, but may be improved in the future by the incorporation of newer combination therapies. For example, a phase II trial in patients with stage I, II and IIIA NSCLC has recently investigated two cycles of induction chemotherapy using paclitaxel and carboplatin before surgery, followed by three cycles of the same regimen. The response rate was 56%, with 86% of patients undergoing a complete resection (i.e. receiving surgery of curative intent) and 56% of patients surviving at 2 years.9
Another recent study has demonstrated the great potential for neoadjuvant chemotherapy in NSCLC. Patients with clinically staged IIIA and IIIB tumours that were considered unsuitable for surgery were recruited and treated with four cycles of gemcitabine and cisplatin. Eighty patients (62%) achieved a partial response of which 40 (31%) were subsequently re-staged and considered suitable for resection. Overall median survival was 19 months.10 Table 2 summarises the use and advantages of adjuvant and neoadjuvant chemotherapy.
| Adjuvant | Neoadjuvant |
| Chemotherapy after surgery ± radiotherapy | Chemotherapy before surgery |
| Stage I, II and IIIA/B | Stage I, II and IIIA/B |
| Survival improved | Survival improved |
References:
1. Gridelli C, Ardizzoni A, Le Chevalier T, et al. Treatment of advanced non-smallcell lung cancer patients with ECOG performance status 2: results of an European Experts Panel. Ann Oncol 2004;15:419–26.
2. Novello S, Le Chevalier T. Chemotherapy for non-small-cell lung cancer. Part 2: Advanced disease. Oncology 2003;17: 457–71.
3. 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.
4. Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004;350:351–60.
5. Hamada C, Ohta M, Wada H, et al. Survival benefit of oral UFT for adjuvant chemotherapy after completely resected non-small-cell lung cancer. Proc Am Soc Clin Oncol 2004;23:615 (Abstract 7000).
6. Gamaz M, Ameur S, Chaouche H, et al. A retrospective analysis to evaluate adjuvant chemotherapy after radical surgery on survival and disease
recurrence in patients with stage I, II, IIIA non-small-cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 2004;23:703 (Abstract 7360).
7. Rosell R, Gomez-Codina J, Camps C, et al. A randomised trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med 1994;330:153–8.
8. Roth JR, Fossella F, Komaki R, et al. A randomised trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. J Natl Cancer Inst 1994;86:673–80.
9. Pisters KM, Ginsberg RJ, Giroux DJ, et al. Induction chemotherapy before surgery for early-stage lung cancer: a novel approach. Bimodality Lung Oncology Team. J Thorac Cardiovasc Surg 2000; 119:429–39.
10. Cappuzzo F, Selvaggi G, Gregorc V, et al. Gemcitabine and cisplatin as induction chemotherapy for patients with unresectable Stage IIIA-bulky N2 and Stage IIIB non-small-cell lung carcinoma: an Italian Lung Cancer Project Observational Study. Cancer 2003; 98:128–34.
