Non-Small Cell Lung Cancer Professional Information

RECURRENT NON-SMALL CELL LUNG CANCER

Many patients with recurrent non-small cell lung cancer (NSCLC) are eligible for clinical trials. Radiation therapy may provide excellent palliation of symptoms from a localized tumor mass.

Patients who present with a solitary cerebral metastasis after resection of a primary NSCLC lesion and who have no evidence of extracranial tumor can achieve prolonged disease-free survival with surgical excision of the brain metastasis and postoperative whole-brain irradiation.[1,2] Unresectable brain metastases in this setting may be treated radiosurgically.[3] Because of the small potential for long-term survival, radiation therapy should be delivered by conventional methods in daily doses of 180 to 200 cGy, while higher daily doses over a shorter period of time (hypofractionated schemes) should be avoided because of the high risk of toxic effects observed with such treatments.[4] Most patients not suitable for surgical resection should receive conventional whole-brain radiation therapy. Selected patients with good performance status and small metastases can be considered for stereotactic radiosurgery.[5]

Approximately one half of patients treated with resection and postoperative radiation therapy will develop recurrence in the brain; some of these patients will be suitable for additional treatment.[6] In those selected patients with good performance status and without progressive metastases outside of the brain, treatment options include reoperation or stereotactic radiosurgery.[3,6] For most patients, conventional radiation therapy can be considered; however, the palliative benefit of this treatment is limited.[7]

A solitary pulmonary metastasis from an initially resected bronchogenic carcinoma is unusual. The lung is frequently the site of second primary malignancies in patients with primary lung cancers. Determining whether the new lesion is a new primary cancer or a metastasis may be difficult. Studies have indicated that in the majority of patients the new lesion is a second primary tumor, and following resection some patients may achieve long-term survival. Thus, if the first primary tumor has been controlled, the second primary tumor should be resected if possible.[8,9]

The use of chemotherapy has produced objective responses and small improvement in survival for patients with metastatic disease.[10] In studies that have examined symptomatic response, improvement in subjective symptoms has been reported to occur more frequently than objective response.[11,12] Informed patients with good performance status and symptomatic recurrence can be offered treatment with a cisplatin-based chemotherapy regimen for palliation of symptoms.

Treatment options:

1. Palliative radiation therapy.

2. Chemotherapy alone. For patients who have not received prior chemotherapy, the following regimens are associated with similar survival outcomes:

cisplatin plus vinblastine plus mitomycin [13]
cisplatin plus vinorelbine [14]
cisplatin plus paclitaxel [15]
cisplatin plus gemcitabine [16]
carboplatin plus paclitaxel [17,18]

3. Surgical resection of isolated cerebral metastasis (highly selected patients).[6]

4. Laser therapy or interstitial radiation therapy for endobronchial lesions.[19]

5. Stereotactic radiosurgery (highly selected patients).[3,5]

1. Patchell RA, Tibbs PA, Walsh JW, et al.: A randomized trial of surgery in the treatment of single metastases to the brain. New England Journal of Medicine 322(8): 494-500, 1990.
2. 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.
3. Loeffler JS, Kooy HM, Wen PY, et al.: The treatment of recurrent brain metastases with stereotactic radiosurgery. Journal of Clinical Oncology 8(4): 576-582, 1990.
4. 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.
5. Alexander E, Moriarty TM, Davis RB, et al.: Stereotactic radiosurgery for the definitive, noninvasive treatment of brain metastases. Journal of the National Cancer Institute 87(1): 34-40, 1995.
6. Arbit E, Wronski M, Burt M, et al.: The treatment of patients with recurrent brain metastases: a retrospective analysis of 109 patients with nonsmall cell lung cancer. Cancer 76(5): 765-773, 1995.
7. Hazuka MB, Kinzie JJ: Brain metastases: results and effects of re-irradiation. International Journal of Radiation Oncology, Biology, Physics 15(2): 433-437, 1988.
8. Salerno TA, Munro DD, Blundell PE, et al.: Second primary bronchogenic carcinoma: life-table analysis of surgical treatment. Annals of Thoracic Surgery 27(1): 3-6, 1979.
9. Yellin A, Hill LR, Benfield JR: Bronchogenic carcinoma associated with upper aerodigestive cancer. Journal of Thoracic and Cardiovascular Surgery 91(5): 674-683, 1986.
10. 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.
11. Ellis PA, Smith IE, Hardy JR, et al.: Symptom relief with MVP (mitomycin C, vinblastine and cisplatin) chemotherapy in advanced non-small-cell lung cancer. British Journal of Cancer 71(2): 366-370, 1995.
12. Medical Research Council Lung Cancer Working Party: Randomized trial of etoposide cyclophosphamide methotrexate and vincristine versus etoposide and vincristine in the palliative treatment of patients with small-cell lung cancer and poor prognosis. British Journal of Cancer 67(Suppl 20): A-4;2, 14, 1993.
13. 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.
14. 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.
15. 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.
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.
17. 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.
18. 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.
19. 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.

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