Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Stage II non-small cell lung cancer (NSCLC) is defined by the following clinical stage groupings:

• T1, N1, M0
• T2, N1, M0
• T3, N0, M0

Surgery is the treatment of choice for patients with stage II NSCLC. Careful preoperative assessment of the patient’s overall medical condition, especially the patient’s pulmonary reserve, is critical in considering the benefits of surgery. Despite the immediate and age-related postoperative mortality rate, a 5% to 8% mortality rate with pneumonectomy or a 3% to 5% mortality rate with lobectomy can be expected.

Patients with inoperable stage II disease and with sufficient pulmonary reserve are candidates for radiation therapy with curative intent.[1] Among patients with excellent performance status, a 3-year survival rate of 20% may be expected if a course of radiation therapy with curative intent can be completed. In the largest retrospective series reported to date, 152 patients with medically inoperable NSCLC, who were treated with definitive radiation therapy, achieved a 5-year overall survival (OS) rate of 10%; however, the 44 patients with T1 tumors achieved an actuarial disease-free survival rate of 60%. This retrospective study also suggested that improved disease-free survival was obtained with radiation therapy doses larger than 60 Gy.[2] Primary radiation therapy should consist of approximately 60 Gy delivered with megavoltage equipment to the midplane of the volume of the known tumor using conventional fractionation. A boost to the cone down field of the primary tumor is frequently used to enhance local control. Careful treatment planning with precise definition of target volume and avoidance of critical normal structures, to the extent possible, is needed for optimal results; this requires the use of a simulator.

After surgery, many patients develop regional or distant metastases.[3] Prospective randomized trials evaluating the role of postoperative adjuvant chemotherapy in patients with NSCLC have been performed for decades. A meta-analysis of adjuvant chemotherapy trials showed a hazard ratio (HR) for death of 0.87 for patients treated with cisplatin-based chemotherapy;[4] however, this result was not statistically significant. Four large randomized trials and an additional meta-analysis evaluating the benefit of adjuvant cisplatin combination chemotherapy have also been reported. Three of the trials and the meta-analysis have shown that adjuvant cisplatin-based chemotherapy improves OS in selected NSCLC patients.

In the largest trial, the International Adjuvant Lung Cancer Trial (IALT), 1,867 patients with resected stage I, stage II, or stage III NSCLC were randomly assigned to cisplatin combination chemotherapy or follow-up.[5] Patients assigned to chemotherapy had a significantly higher survival rate than those assigned to observation (5-year survival 44.5% vs. 40.4%, HR for death = 0.86; 95% confidence interval [CI], 0.76–0.98; P < .03).[5][Level of evidence: 1iiA] Seven patients (0.8%) died of chemotherapy-induced toxic effects.

In the second trial (INT- JBR-10), 482 patients with completely resected stage I (T2, N0) or stage II (excluding T3, N0) NSCLC were randomly assigned to receive four cycles of vinorelbine and cisplatin or observation.[6] OS was significantly prolonged for patients receiving chemotherapy (median 94 months vs. 73 months; HR = 0.69; P = .011).[6][Level of evidence: 1iiA] Two patients died of drug-related toxic effects.

In the third trial (CALGB-9633), 344 patients with stage IB (T2, N0, M0) NSCLC were randomly assigned to four cycles of paclitaxel and carboplatin or observation.[7] There were no chemotherapy-related toxic deaths. The hazard ratio for death was significantly lower among patients receiving adjuvant chemotherapy (HR = 0.62; 95% CI, 0.41–0.95; P = .028).[7][Level of evidence: 1iiA] OS at 4 years was 71% (95% CI, 62%–81%) in the chemotherapy group and 59% (95% CI, 50%–69%) in the observation group.

In the fourth trial, the Adjuvant Lung Project Italy trial, 1,209 patients with stage I, stage II, or stage IIIA NSCLC were randomly assigned to receive mitomycin C, vindesine, and cisplatin every 3 weeks, or no treatment after complete resection.[8][Level of evidence: 1iiA] After a median follow-up time of 64.5 months, there was no statistically significant difference between the two patient groups in OS (HR = 0.96; 95% CI, 0.81–1.13; P = .589) or progression-free survival (HR = 0.89; 95% CI, 0.76–1.03; P = .128).

The literature-based meta-analysis of randomized trials identified 11 trials conducted on a total of 5,716 patients. This analysis includes the IALT and ALPI trials noted above. In this analysis, HR estimates suggested that adjuvant chemotherapy yielded a survival advantage over surgery alone (HR = 0.872; 95% CI, 0.805–0.944; P = .001). In a subset analysis, both cisplatin-based chemotherapy (HR = 0.891; 95% CI, 0.815–0.975; P = .012) and single-agent therapy with tegafur and uracil (UFT) (HR = 0.799; 95% CI, 0.668–0.957; P = .015) were found to yield a significant survival benefit.[9,10]

In summary, the preponderance of evidence indicates that adjuvant cisplatin combination chemotherapy provides a significant survival advantage to patients with resected NSCLC. The optimal sequence of surgery and chemotherapy and the benefits and risks of adjuvant radiation therapy in patients with resectable NSCLC remain to be determined.

Treatment options:

1. Lobectomy; pneumonectomy; or segmental, wedge, or sleeve resection as appropriate.



2. Radiation therapy with curative intent (for potentially operable tumors in patients with medical contraindications to surgery).



3. Adjuvant chemotherapy with or without other modalities after curative surgery.[5-10]



4. Clinical trials of radiation therapy after curative surgery.[11]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage II non-small cell lung cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Komaki R, Cox JD, Hartz AJ, et al.: Characteristics of long-term survivors after treatment for inoperable carcinoma of the lung. Am J Clin Oncol 8 (5): 362-70, 1985.  [PUBMED Abstract]
   
   
2. Dosoretz DE, Katin MJ, Blitzer PH, et al.: Radiation therapy in the management of medically inoperable carcinoma of the lung: results and implications for future treatment strategies. Int J Radiat Oncol Biol Phys 24 (1): 3-9, 1992.  [PUBMED Abstract]
   
   
3. Martini N, Bains MS, Burt ME, et al.: Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg 109 (1): 120-9, 1995.  [PUBMED Abstract]
   
   
4. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group. BMJ 311 (7010): 899-909, 1995.  [PUBMED Abstract]
   
   
5. Arriagada R, Bergman B, Dunant A, et al.: Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 350 (4): 351-60, 2004.  [PUBMED Abstract]
   
   
6. Winton TL, Livingston R, Johnson D, et al.: 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.10. [Abstract] J Clin Oncol 22 (Suppl 14): A-7018, 621s, 2004. 
   
   
7. 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. [Abstract] J Clin Oncol 22 (Suppl 14): A-7019, 621s, 2004. 
   
   
8. 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 95 (19): 1453-61, 2003.  [PUBMED Abstract]
   
   
9. 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 22 (19): 3860-7, 2004.  [PUBMED Abstract]
   
   
10. 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 350 (17): 1713-21, 2004.  [PUBMED Abstract]
    
    
11. Holmes EC: Adjuvant treatment in resected lung cancer. Semin Surg Oncol 6 (5): 263-7, 1990.  [PUBMED Abstract]
    
    

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