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Chemotherapy plus Radiotherapy Compared with Radiotherapy Alone in the Treatment of Locally Advanced, Unresectable, Non-Small-Cell Lung Cancer: A Meta-Analysis

Robert S. Pritchard, MD, MS; and Stephen P. Anthony, DO
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From the Department of Veterans Affairs Medical Center, White River Junction, Vermont; and the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. Disclaimer: Any opinions expressed herein are those of the authors and do not represent the opinions or policies of the Department of Veterans Affairs or the Dartmouth Medical School. Acknowledgment: The authors thank H. Gilbert Welch, MD, MPH, for his assistance and advice and for reviewing multiple drafts of this manuscript. Grant Support: By Veterans Affairs Health Services Research and Development Merit Review Award 92-002 (Dr. Welch). Requests for Reprints: Robert S. Pritchard, MD, Department of Medicine (111), Department of Veterans Affairs Medical Center, White River Junction, VT 05009. Current Author Addresses: Dr. Pritchard: Department of Medicine (111), Department of Veterans Affairs Medical Center, White River Junction, VT 05009.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1996;125(9):723-729. doi:10.7326/0003-4819-125-9-199611010-00003
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Background: Survival of patients with locally advanced, unresectable (stage III), non-small-cell lung cancer treated with radiotherapy is poor. Trials of the addition of chemotherapy to radiotherapy have produced conflicting results.

Objective: To compare chemotherapy plus radiotherapy with radiotherapy alone in patients with stage III, non-small-cell lung cancer.

Data Sources: English-language journal articles published between 1987 and 1995 identified in a MEDLINE search.

Study Selection: Randomized trials that reported survival after previously untreated patients received chemotherapy plus radiotherapy or radiotherapy alone were reviewed.

Data Extraction: For all eligible articles, reported survival curves were used to determine the relative risk for death in each of 3 years. These data were combined to determine a pooled estimate of the relative risk for death at 1, 2, and 3 years.

Data Synthesis: Fourteen articles reporting on a total of 2589 patients were reviewed. Compared with radiotherapy, the combination of chemotherapy and radiotherapy reduced the risk for death at 1 year (relative risk, 0.88 [95% CI, 0.80 to 0.96]), 2 years (relative risk, 0.87 [CI, 0.81 to 0.94]), and 3 years (relative risk, 0.83 [CI, 0.77 to 0.90]). This corresponded to a mean gain in life expectancy of about 2 months. The magnitude of the treatment effect was similar when trials of concurrently and sequentially administered chemotherapy were considered separately.

Conclusion: The addition of chemotherapy to radiotherapy improves survival in patients with locally advanced, unresectable, non-small-cell lung cancer. The absolute benefit is relatively small, however, and should be balanced against the increased toxicity associated with the addition of chemotherapy.

Figures

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Figure 1. The 1-, 2-, and 3-year relative risks for death and 95% CIs are shown for each study (numbers in parentheses are reference numbers). The results of the meta-analysis pooled across all studies and only those in which cisplatin was part of the chemotherapeutic regimen are also shown. Two studies allowed two comparisons: The study by Schaake-Koning and colleagues was a three-group comparison of cisplatin administered weekly (w) or daily (d) with radiotherapy compared with radiotherapy alone, and the trial by Jeremic and colleagues was a three-group comparison of two different schedules of chemotherapy (II and III) plus radiotherapy compared with radiotherapy alone. The trials by van Houtte and colleagues, Mattson and colleagues, and Soresi and colleagues did not present 3-year survival data and thus are not included in the pooled estimated of the effect of combined therapy at 3 years.
Chemotherapy plus radiotherapy compared with radiotherapy alone for the treatment of locally advanced, unresectable, non-small-cell lung cancer.
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Figure 2. The relative risk represents the risk for death during that period conditional on being alive at the start of that period. The number of patients across all studies who were estimated to be at risk at the start of the period is shown on the right side of the figure.
Pooled relative risk for death in locally advanced, unresectable, non-small-cell lung cancer and 95% CI for each 6-month period.
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Figure 3.
Cumulative survival probabilities in patients with locally advanced, unresectable, non-small-cell lung cancer treated with chemotherapy plus radiotherapy (solid line) and radiotherapy alone (dashed line).
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