Non-Small Cell Lung Cancer Professional Information

STAGE IV NON-SMALL CELL LUNG CANCER

Cisplatin-containing and carboplatin-containing combination chemotherapy regimens produce objective response rates (including a few complete responses) that are higher than those achieved with single-agent chemotherapy. Although toxic effects may vary, outcome is similar with most cisplatin-containing regimens; a randomized trial comparing 5 cisplatin-containing regimens showed no significant difference in response, duration of response, or survival.[1] Patients with good performance status and a limited number of sites of distant metastases have superior response and survival when given chemotherapy when compared to other patients.[2] A prospective randomized comparison of vinorelbine plus cisplatin versus vindesine plus cisplatin versus single agent vinorelbine has reported improved response rate (30%) and median survival (40 weeks) with the vinorelbine plus cisplatin regimen.[3] Two small phase II studies reported that paclitaxel (Taxol) has single-agent activity in stage IV patients, with response rates in the range of 21% to 24%.[4,5] Reports of paclitaxel combinations have shown relatively high response rates, significant 1 year survival, and palliation of lung cancer symptoms.[6] With the paclitaxel plus carboplatin regimen, response rates have been in the range of 27% to 53% with 1-year survival rates of 32% to 54%.[6,7] The combination of cisplatin and paclitaxel was shown to have a higher response rate than the combination of cisplatin and etoposide.[8] Additional clinical studies should better define the role of these newer combination chemotherapy regimens in the treatment of advanced non-small cell lung cancer.[8] Meta-analyses have shown that chemotherapy produces modest benefits in short-term survival compared to supportive care alone in patients with inoperable stages IIIb and IV disease.[9-11]

Although these results support further evaluation of chemotherapeutic approaches for both metastatic and locally advanced non-small cell lung cancer (NSCLC), efficacy of current programs is such that no specific regimen can be regarded as standard therapy. Appropriate patients should be encouraged to participate in clinical trials. Outside of a clinical trial setting, chemotherapy should be given only to patients with good performance status and evaluable tumor lesions who desire such treatment after being fully informed of its anticipated risks and limited benefits.

Radiation therapy may be effective in palliating symptomatic local involvement with NSCLC such as tracheal, esophageal, or bronchial compression, bone or brain metastases, pain, vocal cord paralysis, hemoptysis, or superior vena cava syndrome. In some cases, endobronchial laser therapy and/or brachytherapy has been used to alleviate proximal obstructing lesions.[12] Such therapeutic intervention may be critical in the prolongation of an acceptable lifestyle in an otherwise functional patient. In the rare patient with synchronous presentation of a resectable primary tumor in the lung and a single brain metastasis, surgical resection of the solitary brain lesion is indicated with resection of the primary tumor and appropriate postoperative chemotherapy and/or irradiation of the primary tumor site and with postoperative whole-brain irradiation delivered in daily fractions of 180-200 cGy to avoid long-term toxic effects to normal brain tissue.[13,14]

In asymptomatic patients kept under close observation, treatment may often be appropriately deferred until symptoms or signs of progressive tumor develop.

Treatment options:

1. External-beam radiation therapy, primarily for palliative relief of local symptomatic tumor growth.

2. Chemotherapy. The following regimens are associated with similar survival outcomes:

cisplatin plus vinblastine plus mitomycin [15]
cisplatin plus vinorelbine [3]
cisplatin plus paclitaxel [8]
cisplatin plus gemcitabine [16]
carboplatin plus paclitaxel [6,7]

3. Clinical trials evaluating the role of new chemotherapy regimens. Refer to the clinical trials section of PDQ for a list of clinical trials. The clinical trials in PDQ are also available on CancerNet (http://cancernet.nci.nih.gov).

4. Endobronchial laser therapy and/or brachytherapy for obstructing lesions.[12]

1. Weick JK, Crowley J, Natale RB, et al.: A randomized trial of five cisplatin-containing treatments in patients with metastatic non-small-cell lung cancer: a Southwest Oncology Group study. Journal of Clinical Oncology 9(7): 1157-1162, 1991.
2. O'Connell JP, Kris MG, Gralla RJ, et al.: Frequency and prognostic importance of pretreatment clinical characteristics in patients with advanced non-small-cell lung cancer treated with combination chemotherapy. Journal of Clinical Oncology 4(11): 1604-1614, 1986.
3. Le Chevalier T, Brisgand D, Douillard JY, et al.: Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients. Journal of Clinical Oncology 12(2): 360-367, 1994.
4. Chang AY, Kim K, Glick J, et al.: Phase II study of taxol, merbarone, and piroxantrone in stage IV non-small-cell lung cancer: the Eastern Cooperative Oncology Group results. Journal of the National Cancer Institute 85(5): 388-394, 1993.
5. Murphy WK, Fossella FV, Winn RJ, et al.: Phase II study of taxol in patients with untreated advanced non-small-cell lung cancer. Journal of the National Cancer Institute 85(5): 384-388, 1993.
6. Johnson DH, Paul DM, Hande KR, et al.: Paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a phase II trial. Journal of Clinical Oncology 14(7): 2054-2060, 1996.
7. Langer CJ, Leighton JC, Comis RL, et al.: Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer: a phase II toxicity, response, and survival analysis. Journal of Clinical Oncology 13(8): 1860-1870, 1995.
8. Bonomi P, Kim K, Chang A, et al.: Phase III trial comparing etoposide (E) cisplatin (C) versus taxol (T) with cisplatin-G-CSF(G) versus taxol-cisplatin in advanced non-small cell lung cancer. An Eastern Cooperative Oncology Group (ECOG) trial. Proceedings of the American Society of Clinical Oncology 15: A-1145, 382, 1996.
9. Souquet PJ, Chauvin F, Boissel JP, et al.: Polychemotherapy in advanced non small cell lung cancer: a meta-analysis. Lancet 342(8862): 19-21, 1993.
10. Grilli R, Oxman AD, Julian JA: Chemotherapy for advanced non-small-cell lung cancer: how much benefit is enough? Journal of Clinical Oncology 11(10): 1866-1872, 1993.
11. Marino P, Pampallona S, Preatoni A, et al.: Chemotherapy vs supportive care in advanced non-small-cell lung cancer: results of a meta-analysis of the literature. Chest 106(3): 861-865, 1994.
12. Miller JI, Phillips TW: Neodymium:YAG laser and brachytherapy in the management of inoperable bronchogenic carcinoma. Annals of Thoracic Surgery 50(2): 190-196, 1990.
13. Mandell L, Hilaris B, Sullivan M, et al.: The treatment of single brain metastasis from non-oat cell lung carcinoma: surgery and radiation versus radiation therapy alone. Cancer 58(3): 641-649, 1986.
14. DeAngelis LM, Mandell LR, Thaler HT, et al.: The role of postoperative radiotherapy after resection of single brain metastases. Neurosurgery 24(6): 798-805, 1989.
15. Veeder MH, Jett JR, Su JQ, et al.: A phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and cisplatin for metastatic squamous cell lung carcinoma. Cancer 70(9): 2281-2287, 1992.
16. Rosell R, Tonato M, Sandler A: The activity of gemcitabine plus cisplatin in randomized trials in untreated patients with advanced non-small cell lung cancer. Seminars in Oncology 25(4 suppl 9): 27-34, 1998.

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