Chest
Chemotherapeutic Management of Stage IV Non-small Cell Lung Cancer*
Section snippets
Are There Identifiable Prognostic Factors That Should Be Used When Selecting Patients for Systemic Chemotherapy?
The prognosis of patients with advanced NSCLC is poor. Most large phase III trials have shown a median survival time of 8 to 10 months and a 1-year survival rate of 30 to 35%.2 Given the consistent improvement in the survival of patients who have been treated with chemotherapy over those receiving supportive care alone, clinicians struggle to stratify these patients into different prognostic groups. One would like to identify those patients who are the most likely to benefit from aggressive
What Is the Evidence That Platinum-Based Chemotherapy Improves Survival?
Ten randomized clinical trials have been published23242526272829303132 comparing platinum-based chemotherapy to best supportive care (BSC) [Table 2]. It should be noted that BSC in these trials included aggressive symptom management (eg, antitussive agents, supplemental oxygen, and nonnarcotic and narcotic analgesic agents) as well as palliative radiotherapy when indicated. In all 10 trials, the median survival time of the treated patients was numerically superior to that of patients receiving
Do “New Agents” Improve Survival as Single Agents Compared to BSC?
Since 1990, several new agents with significant single-agent activity in NSCLC have been developed including paclitaxel, docetaxel, vinorelbine, gemcitabine, and irinotecan. These agents are commonly referred to as third-generation agents. Several randomized trials have been reported in which these new agents were tested against BSC using survival as the primary end point (Table 5). Both taxanes (ie, paclitaxel and docetaxel) have been compared to BSC in a randomized trial.3739 Survival was
Do the New Agents in Combination With the Platinum-Based Agents Improve Survival Over Second-Generation Platinum-Based Regimens?
As noted above, a number of new chemotherapy agents (ie, paclitaxel, docetaxel, gemcitabine, vinorelbine, and irinotecan) have been identified over the last 10 years as having documented activity in patients with advanced NSCLC. These third-generation agents have been incorporated into clinical trials and have been reported to have an improved toxicity profile, but is there proof that these new drugs also improve survival compared to older standard therapies?
The first of the new drugs to be
Is There a Standard of Care Regarding the Choice of Chemotherapy in the First-Line Setting?
Two large randomized trials that were reported within the last 2 years compared several of the new-generation regimens in the treatment of patients with advanced NSCLC. The first trial,58 conducted by the Southwest Oncology Group, compared the use of cisplatin-vinorelbine with carboplatin-paclitaxel. There was no difference in objective response, median survival time, or 1-year survival rates between patients receiving the two combinations. The second trial,59 by ECOG, compared
Is There an Optimal Duration of Chemotherapy?
Given the noncurative nature of stage IV NSCLC, the duration of chemotherapy must be weighed against the toxicity it engenders. Until recently, few trials addressed this issue, and chemotherapy would be administered for six or more cycles. In the 1997 guideline issued by the American Society of Clinical Oncology,61 the lack of data pertaining to this issue was cited. The consensus of the expert panel was that chemotherapy should be administered for no more than eight cycles in patients with
Does Second-Line Chemotherapy Improve Survival?
Since the first-line therapy used in patients with stage IV NSCLC is not curative, patients will eventually experience disease progression unless they develop another fatal comorbid illness. Once the disease progresses, the median survival time is approximately 3 months. The proportion of patients receiving second-line therapy following disease progression after receiving first-line platinum-based therapy has not been well-described but is generally < 50%.4248 Many of these patients retain a
Is There Evidence To Support the Use of Chemotherapy To Relieve Symptoms and Improve QOL?
The majority of patients with advanced NSCLC are symptomatic at some point as a result of their disease.71 Symptoms may be either disease-specific (eg, cough, hemoptysis, chest pain, or dyspnea) or disease-nonspecific (eg, weight loss, malaise, or declining PS).
At least seven studies72737475767778 have documented palliation of symptoms by chemotherapy in patients with advanced NSCLC (Table 7). These phase II studies generally have reported percentages of patients with a specific symptom in whom
What Are Patients' Preferences and Attitudes Toward Chemotherapeutic Treatment Options for Advanced NSCLC?
Two descriptive studies utilizing cancer patients who previously had been treated addressed the issue of patient preferences and attitudes toward receiving palliative cisplatin-based chemotherapy compared to BSC for survival and/or QOL benefit. Using a time-tradeoff technique, 60 patients were interviewed to address attitudes toward the improved median survival time and 1-year survival rate for the addition of cisplatin chemotherapy and BSC compared to BSC alone. Attitudes ranged from
Is There Any Evidence That Would Support Who Administered the Chemotherapy Made a Difference?
The MEDLINE search addressing this issue yielded no citations that were relevant with regard to addressing this question. Since the evaluation of NSCLC patients for chemotherapy requires an understanding of its indication as well as the proper selection of patients, physicians performing these duties should have experience and specialized training. This specialized training also should include experience with the proper administration of chemotherapy protocols as well as a working knowledge of
What Are the Outcome Expectations and Adverse Effects Seen With Chemotherapy and How Do They Compare With the Natural History?
The natural history of untreated stage IV NSCLC is best documented in the randomized trials of chemotherapy vs BSC ((Tables 2and 5). The impact that chemotherapy has on survival is significant and has been discussed in the previous sections. When QOL has been examined, patients receiving chemotherapy report better scores compared to patients receiving only BSC,313239 supporting the contention that the disease is worse than the treatment. The expectations regarding survival and toxicity when
Conclusion
Chemotherapy improves survival and palliates symptoms, thereby improving QOL in patients with stage IV NSCLC in both the first-line and second-line setting. Selecting patients based on PS is important as patients significantly compromised by their disease may not benefit from therapy and may experience excessive toxicity. Both platinum-based regimens as well as individual single-agent regimens have an impact on survival. However, platinum-based combination regimens using the new
Summary of Recommendations
- 1.
When selecting patients for systemic chemotherapy, PS at the time of diagnosis should be used because it is a consistent prognostic factor for survival. Patients with a PS (PS) of ECOG 0 or 1 should be offered chemotherapy (level of evidence, good; benefit, substantial; grade of recommendation, A). Data are not yet sufficient to routinely recommend chemotherapy to patients with a PS of ECOG level 2 (level of evidence, poor; benefit, small/weak; grade of recommendation, I). Patients with a PS of
Appendix
The following search terms were used in the study: age and lung cancer; antineoplastic agents, combined; carcinoma, non-small cell lung; carcinoma, non-small cell lung/drug therapy; carcinoma, non-small cell lung/therapy; chemotherapy; clinical trials; combination chemotherapy; duration of therapy; lung neoplasms; lung neoplasms/drug therapy; lung neoplasms/therapy; outcomes; performance status and lung cancer; prognosis factors and lung cancer; prognosis and lung cancer; prognosis and
ACKNOWLEDGMENT
Thanks to Lenka Cook for the creation of Figure 2.
References (92)
Cancer facts and figures
Chemotherapy for stage IV non-small cell lung cancer
Revisions in the international system for staging lung cancer
Chest
(1997)- et al.
Survival with inoperable lung cancer: an integration of prognostic variables based on simple clinical criteria
Cancer
(1977) Prognostic factors for survival in patients with inoperable lung cancer
J Natl Cancer Inst
(1980)- et al.
Frequency and prognostic importance of pretreatment clinical characteristics in patients with advanced non-small cell lung cancer treated with combination chemotherapy
J Clin Oncol
(1986) - et al.
Long-term survivors in metastatic non-small cell lung cancer: an Eastern Cooperative Oncology Group study
J Clin Oncol
(1986) - et al.
A randomized trial of the four most active regimens for metastatic non-small cell lung cancer
J Clin Oncol
(1986) - et al.
Combination chemotherapy vs single agents followed by combination chemotherapy in stage IV non-small cell lung cancer: a study of the Eastern Cooperative Oncology Group
J Clin Oncol
(1989) - et al.
Cisplatin vs cisplatin plus etoposide in the treatment of advanced non-small cell lung cancer
J Clin Oncol
(1989)
Randomized comparison of two combination regimens vs minimal chemotherapy in non-small cell lung cancer: a Southeastern Cancer Study Group Trial
J Clin Oncol
Effect of alternating combination chemotherapy on survival of ambulatory patients with metastatic large cell and adenocarcinoma of the lung: a Southwest Oncology Group Study
J Clin Oncol
Survival determinants in extensive-stage non-small cell lung cancer: the Southwest Oncology Group Experience
J Clin Oncol
Adenocarcinoma of the lung in young patients: the MD Anderson experience
Cancer
Two-year survival and prognostic factors for overall survival in advanced NSCLC: an ECOG experience [abstract]
Proc Am Soc Clin Oncol
Is quality of life predictive of survival in patients with advanced NSCLC?
Cancer
Chemotherapy of non-small cell lung cancer according of disease extent: a meta-analysis of the literature
Lung Cancer
Is it time to reevaluate our approach to the treatment of brain metastases in patients with non-small cell lung cancer
Lung Cancer
Chemotherapy with cisplatin and teniposide for cerebral metastases in non-small cell lung cancer
Lung Cancer
Clinical survival predictors in patients with advanced cancer
Arch Intern Med
The use of neuroendocrine immunoperoxidase markers to predict chemotherapy response in patients with non-small cell lung cancer
J Clin Oncol
Clinical characterization of non-small cell lung cancer tumors showing neuroendocrine differentiation features
J Clin Oncol
Chemotherapy can prolong survival in patients with advanced non-small cell lung cancer: report of a Canadian multicenter randomized trial
J Clin Oncol
Supportive care vs supportive care and combination chemotherapy in metastatic non-small cell lung cancer
Cancer
A randomized trial of cisplatin and vindesine vs supportive care only in advanced non-small cell lung cancer
Br J Cancer
La chimiotherapie comportant du cisplatine est elle utile dans le cancer bronchique non microcellulaire au stade IV?: resultats d'une etude ranodmisee
Bull Cancer
A randomized trial of alternating chemotherapy vs best supportive care in advanced non-small cell lung cancer
J Clin Oncol
Symptomatic treatment vs combination chemotherapy for patients with extensive non-small cell lung cancer
Cancer
Cisplatin-cyclophosphamide-mitomycin combination chemotherapy with supportive care vs supportive care alone for treatment of metastatic non-small cell lung cancer
J Natl Cancer Inst
Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only: a multicenter randomized phase III trial
Eur J Cancer
Relationship between quality of life and clinical outcomes in advanced non-small cell lung cancer: best supportive care (BSC) vs BSC plus chemotherapy
Lung Cancer
Mitomycin, ifosfamide, and cisplatin in unresectable non-small cell lung cancer: effects on survival and quality of life
J Clin Oncol
Polychemotherapy in advanced non-small cell lung cancer: a meta-analysis
Lancet
Chemotherapy for advanced non-small cell lung cancer: how much benefit is enough?
J Clin Oncol
Chemotherapy vs supportive care in advanced non-small cell lung cancer: results of a meta-analysis of the literature
Chest
Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomized clinical trials
BMJ
A multicenter, randomized phase III study of docetaxel plus best supportive care vs best supportive care in chemotherapy-naïve patients with metastatic or non-resectable localized non-small cell lung cancer (NSCLC)
Lung Cancer
Effects of vinorelbine on quality of life and survival in elderly patients with advanced non-small cell lung cancer
J Natl Cancer Inst
Randomized trial of paclitaxel plus supportive care vs supportive care for patients with advanced non-small cell lung cancer
J Natl Cancer Inst
Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small cell lung cancer
J Clin Oncol
Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer: a randomized trial with quality of life as the primary outcome
Br J Cancer
Randomized study of vinorelbine and cisplatin vs vindesine and cisplatin versus vinorelbine alone in advanced non-small cell lung cancer: results of a European multicenter trial including 612 patients
J Clin Oncol
Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small cell lung cancer: a Southwest Oncology Group Study
J Clin Oncol
Comparison of survival and quality of life in advanced non-small cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin vs etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial
J Clin Oncol
Randomized phase III trial comparing cisplatin/etoposide vs carboplatin/paclitaxel in advanced non-small cell lung cancer (NSCLC) [abstract]
Proc Am Soc Clin Oncol
Phase III. comparative stud of high-dose cisplatin vs a combination of paclitaxel and cisplatin in patients with advanced non-small cell lung cancer
J Clin Oncol
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