Chest
Volume 117, Issue 4, Supplement 1, April 2000, Pages 123S-126S
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Locally Advanced, Unresectable Non-Small Cell Lung Cancer: New Treatment Strategies

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Approximately 40% of non-small cell lung cancer (NSCLC) patientspresent with locally advanced, unresectable lesions. Treatmentwith thoracic radiotherapy yields survivals averaging just 9 to 10months, and long-term survival at 5 years is poor. Recent studiesindicate that chemotherapy followed by thoracic radiotherapy improves5-year survival by three- to fourfold. Nevertheless, most patients doultimately die of the underlying disease. New strategies designed toenhance local tumor control—use of radiation-sensitizing drugs, three-dimensional treatment planning techniques, or altered radiationfractionation schedules—may further improve survival outcome. Inaddition, newer cisplatin-based regimens containing either paclitaxelor vinorelbine improve survival over that achieved with older vincaalkaloid or podophyllotoxin combination regimens. Accordingly, thenewer drug regimens combined with radiotherapy can be expected tofurther improve survival in this subset of NSCLC patients. Prospectivestudies are underway to test this conjecture.

Section snippets

Current Management of Locally Advanced, Unresectable NSCLC

Approximately 40% of patients with newly diagnosed NSCLC first present with locally advanced disease, and the majority are inoperable.1 Traditionally, these patients were treated with radiotherapy alone, resulting in a median survival of approximately 9 to 10 months and a 5-year survival rate of approximately 7%.7 These discouraging results were largely due to the eventual development of extrathoracic metastases. Several investigators have tried combining local therapy (ie, radiotherapy) with

Improving Local Tumor Control

Although combined-modality treatment with chemotherapy and radiotherapy has improved survival in some patients with stage III NSCLC, most still succumb to the underlying disease.1 Tumor progression remains problematic, both locally within the chest and in extrathoracic sites. We will first examine the problem of local tumor control.

It is commonly estimated that radiotherapy alone affords intrathoracic control in up to 50% of NSCLC cases, provided a total dose ≥ 60 Gy is employed.11 However,

Improved Control of Systemic Disease

Several meta-analyses clearly showed that cisplatin-based chemotherapy can improve survival in patients with NSCLC.2, 35, 36 The modest survival advantage benefits primarily those patients treated with cisplatin-based combination regimens, although there is a trend toward improved survival with regimens containing vinca alkaloids or etoposide.2 Within the past few years, several new drugs have shown excellent activity against NSCLC, including the taxanes (paclitaxel and docetaxel), vinorelbine,

Summary

In summary, better local control, as well as greater control of extrathoracic micrometastases, should result in improved survival among patients with locally advanced NSCLC. The methods of improving local control are quite varied, and each merits continued investigation. Potentially, these techniques will lead to further improvement in the survival of NSCLC patients with locally advanced disease.

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