Chest
Volume 132, Issue 3, Supplement, September 2007, Pages 277S-289S
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DIAGNOSIS AND MANAGEMENT OF LUNG CANCER: ACCP GUIDELINES (2ND EDITION)
Treatment of Non-small Cell Lung Cancer, Stage IV: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)

https://doi.org/10.1378/chest.07-1381Get rights and content

Background

Stage IV non-small cell lung cancer (NSCLC) remains a treatable but incurable disease.

Methods

A MEDLINE search was performed to identify pertinent peer-reviewed articles that addressed the questions posed for this section. The writing committee developed and graded recommendations, which were subsequently approved by the American College of Chest Physicians.

Results

Platinum-based doublets remain the standard of care in patients with good performance status (PS); there is no evidence that the addition of a third cytotoxic agent improves survival. Likewise, with only one exception, the addition of a new targeted or biological agent to platinum-based doublets does not improve survival. The one exception is the addition of bevacizumab, an antiangiogenic agent, to carboplatin/paclitaxel in patients with stage IV disease and good PS. Patients for whom bevacizumab is recommended must also be selected on the basis of histology (nonsquamous), absence of brain metastases and hemoptysis, and no indication for therapeutic anticoagulation. In patients with stage IV NSCLC and PS of 2, chemotherapy is recommended, but the optimal approach has not been defined. Elderly patients, defined as ≥ 70 years old, also derive benefit from chemotherapy. Most elderly patients should receive single-agent chemotherapy, but elderly patients with good PS and without significant comorbidities seem to derive a similar benefit from platinum-based doublets compared with their younger counterparts without a prohibitive difference in treatment toxicities. Because stage IV NSCLC is incurable, quality-of-life issues are important, and tools exist to monitor a patient's quality of life during therapy. Last, patients need to be informed of the implication of the diagnosis of stage IV NSCLC and be educated about treatment options that are available to them.

Conclusions

Advances have been made in stage IV NSCLC, and the appropriate use of chemotherapy continues to evolve on the basis of well-designed clinical trials that address critical issues in this population.

Section snippets

Materials and Methods

In light of the recommendations made in 2003, additional questions that were believed to be pertinent to patients with advanced stage IIIB/IV NSCLC were asked. A systematic review of the literature was undertaken by the multidisciplinary writing committee to identify published materials, including both original articles and guidelines, that address lung cancer diagnosis, management, and treatment. Materials that are appropriate to this topic were obtained by literature search of a computerized

Is There an Advantage to Using Three Chemotherapeutic Agents Compared With Two in Patients With Stage IV NSCLC and Good PS?

The 2003 ACCP recommendations defined platinum-based doublets as the standard of care for patients with stage IV NSCLC and good PS.3 Delbaldo et al4 reported a metaanalysis that included 13,601 patients in 65 trials and showed that two chemotherapeutic agents led to superior response and survival rates in patients with stage IV NSCLC compared with single agents (Table 2). Since the report of that metaanalysis, platinum-based doublets were shown to be superior to single-agent therapy in three

Recommendations

1. In patients with stage IV NSCLC and good PS, two-drug combination chemotherapy is recommended. The addition of a third cytotoxic chemotherapeutic agent is not recommended because it provides no survival benefit and may be harmful. Grade of recommendation, 1A

2. Bevacizumab improves survival combined with carboplatin and paclitaxel in a clinically selected subset of patients with stage IV NSCLC and good PS (nonsquamous histology, lack of brain metastases, and no hemoptysis). In these patients,

Recommendations

3. In patients who have stage IV NSCLC and are elderly (≥ 70 to 79 years old), single-agent chemotherapy is recommended for most. Grade of recommendation, 1A

4. However, in patients who have stage IV NSCLC, are elderly (≥ 70 to 79 years old), have good PS, and lack significant comorbidities, two-drug combination chemotherapy is recommended as an option. Grade of recommendation, 1B

5. In patients who have stage IV NSCLC and are ≥ 80 years old, the benefit of chemotherapy is unclear and should be

Recommendations

6. In patients with stage IV NSCLC and a PS of 2, chemotherapy is recommended on the basis of defined response rates and symptom palliation. Grade of recommendation, 1B

7. In patients with stage IV NSCLC and a PS of 2, no specific recommendation can be given with regard to the optimal chemotherapeutic strategy. A single phase III trial showed a survival benefit to a carboplatin-based doublet compared with a single agent in a prospectively planned subset analysis. Grade of recommendation, 2C

Recommendation

8. It is recommended that patient-reported HRQOL be measured using the FACT-L or EORTC QLQ-C30 questionnaire because it is a significant prognostic factor for survival. Grade of recommendation, 1A

Recommendation

9. It is recommended that patients with stage IV NSCLC receive adequate education about the risks and benefits of chemotherapy to enable active participation in the decision-making process regarding treatment selection. Grade of recommendation, 1C

Conclusions

The standard of care for the treatment of the patient with stage IV NSCLC and good PS remains doublet-based therapy, with the exception of patients who are eligible to receive bevacizumab, which has been shown in a large, randomized, phase III trial to improve survival over chemotherapy alone. Elderly patients (≥ 70 to 79 years old) also benefit from therapy, as do patients with poor PS. These populations are heterogeneous, and the optimal approach in these patients remains controversial and

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    The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml)

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