Results of Clinical Trials for Locally
Advanced and Metastatic Nonsmall-Cell
Lung Cancer
Sakkaraiappan Ramalingam and Chandra P. Belani
Chemotherapy in nonsmall-cell lung cancer (NSCLC) is not just a reality but has resulted in important
improvements in quality of life and survival for patients with locally advanced and metastatic NSCLC.
For patients with stage IV NSCLC, platinum-based 2-drug combinations are superior to single-agent
therapy and have a superior therapeutic index than 3-drug combinations. Concurrent chemoradiation
has become the standard of care for patients with locally advanced NSCLC. The addition of consoli-
dation chemotherapy following definitive chemoradiation appears to improve median survival. The era
of molecularly targeted therapies for NSCLC is here. Early results with some of the targeted agents
studied for the treatment of NSCLC have generated a great deal of excitement. In this article, we review
the results of recent clinical trials in locally advanced and metastatic NSCLC.
© 2003 Elsevier Inc. All rights reserved.
Key words: Nonsmall-cell lung cancer, chemotherapy, radiation, chemoradiation, molecularly targeted
therapy
L
ung cancer is the leading cause of cancer-
related mortality in the United States. Ap-
proximately 169,400 new cases of lung cancer will
be diagnosed in the year 2002 in the United
States.
1
Nonsmall-cell lung cancer (NSCLC) ac-
counts for approximately 80% of all lung cancers.
A majority of the patients with NSCLC will
present with locally advanced/metastatic disease,
which is not amenable to surgical resection. Even
with early stage lung cancer (with the exception
of T1N0 disease) that is surgically resected, re-
currence of disease will develop in more than 50%
of the patients.
2
Treatment for patients with
stage IV disease is systemic chemotherapy, while
those with locally advanced disease benefit from
combined modality treatment approaches con-
sisting of radiation therapy and chemotherapy
with or without surgical intervention.
Several important advances have been made
in the treatment of patients with NSCLC in re-
cent years. These advances include improved ra-
diation techniques and incorporation of newer
chemotherapy agents into treatment regimens,
resulting in improved efficacy with more favor-
able toxicity profile. Identification of molecular
targets and novel agents that can modulate these
targets to retard the progression of malignancy
are presently undergoing evaluation. In this arti-
cle, we will review the recent clinical trials in
patients with locally advanced and metastatic
NSCLC.
Locally Advanced Unresectable NSCLC
Clinical trials conducted in the 1970s established
the efficacy of radiation therapy in patients with
locally advanced NSCLC. The optimal dose of
radiation was determined to be 60 Gy adminis-
tered in a 2Gy/fraction over 6 weeks.
3
Despite
undergoing definitive radiation, patients had a
high incidence of local and distant relapse. This
led to the initiation of trials that studied the
effect of adding chemotherapy in addition to ra-
diation. Chemotherapy was thought to act in
multiple ways that included radiation-sensitiza-
tion of cancer cells in the field of radiation and
cytotoxic effect on micrometastatic disease. The
Cancer and Leukemia group B 8433 trial evalu-
ated the use of addition of induction chemother-
apy to patients undergoing radiation therapy for
From the Division of Hematology-Oncology, University of Pitts-
burgh School of Medicine, and Lung Cancer Program, University of
Pittsburgh Cancer Institute, Pittsburgh, PA.
Address reprint requests to Chandra P. Belani, MD, UPMC
Cancer Pavilion, Suite 570, 5150 Center Avenue, Pittsburgh, PA
15232. E-mail: belanicp@msx.upmc.edu
© 2003 Elsevier Inc. All rights reserved.
1043-0679/03/1504-0015$30.00/0
doi:10.1053/S1043-0679(03)00097-2
438
Seminars in Thoracic and Cardiovascular Surgery, Vol 15, No 4 (October), 2003: pp 438-447