Advances in Treating Lung Cancer
Survival rates for lung cancer are poor,
which is why developing new ways to treat the disease—or
prevent it altogether—is so important.
Lung cancer is the most dangerous type of cancer, killing 85%
of people within five years of diagnosis. “Lung cancer
causes more deaths in women than breast and ovarian cancer combined,
and more than three times more deaths in men than prostate cancer,” emphasizes
Julie Brahmer, M.D., an assistant professor at Hopkins’s
Sidney Kimmel Comprehensive Care Center.
But effective treatments for lung cancer do exist, with those
that can extend survival by even a few months representing a
significant advance in treatment. Treating lung cancer also can
improve quality of life.
Here’s an overview of the newest treatments for lung cancer,
along with a look at drugs that are under development to treat
or even prevent the disease.
New Combinations and Agents
Several new chemotherapy regimens for lung cancer have been
developed in the last few years, and one drug has been approved.
New regimens. About 80% of lung
cancers are non-small cell lung cancers. Treatment for this type
of cancer usually consists of surgery followed by chemotherapy
and, sometimes, radiation. In some cases, chemotherapy and radiation
are used to shrink the tumor prior to surgery.
The drug cisplatin (Platinol) used to be the standard treatment
for non-small cell lung cancer. Now, a second drug—such
as gemcitabine (Gemzar), vinorelbine (Navelbine), paclitaxel
(Taxol), or docetaxel (Taxotere)—is added to boost cisplatin’s
effectiveness. In addition, a less toxic drug called carboplatin
(Paraplatin) sometimes is substituted for cisplatin. Like most
chemotherapy regimens, these combinations usually cause temporary
but severe side effects that may include nausea, vomiting, loss
of appetite, hair loss, mouth sores, severe diarrhea, fatigue,
and low resistance to infection.
Other regimens for non-small cell lung cancer are also being
examined, such as gemcitabine (Gemzar) in combination with vinorelbine
(Navelbine) or paclitaxel. Another combination that has shown
promise in Japanese trials is uracil and tegafur, neither of
which has been approved in the United States. The hope is that
these combinations might be just as effective as older combinations,
but less toxic. Also being studied is becavizumab (Avastin),
a drug that was recently approved for treating colon cancer,
to see if it can extend survival when added to carboplatin and
Small cell lung cancer accounts for the remaining 20% of lung
cancers. Surgery is ineffective for this type of lung cancer,
but chemotherapy and radiation are often used together for limited
disease; chemotherapy alone is used for extensive disease.
Cisplatin plus etoposide (VePesid, Etopophos, Toposar) is usually
considered the optimal chemotherapy regimen for small cell lung
cancer. However, a Japanese study found that substituting irinotecan
(Camptosar) for etoposide improved survival from 9.4 months to
12.8 months among people with metastatic disease (cancer that
has spread beyond the lungs). Three randomized controlled trials
are under way to test this finding. Researchers are also examining
gemcitabine, paclitaxel, vinorelbine, and topotecan (Hycamtin)
in combination with cisplatin for use in small cell lung cancer.
Gefitinib (Iressa). A new option
for people with non-small cell lung cancer that doesn’t
respond to conventional chemotherapy is gefitinib, which was
approved in 2003. In one study of 142 people whose tumors didn’t
respond to two or more types of chemotherapy, 11% had a response
to gefitinib. This response lasted for at least seven months
in half the people. It is unknown whether this response will
translate into fewer cancer-related symptoms or longer survival.
Unfortunately, attempts to boost the effectiveness of standard
chemotherapy by adding gefitimib have been disappointing.
Gefitimib is taken by mouth and usually produces only minor
side effects, such as diarrhea, rash, acne, and dry skin. It
can also cause nausea and vomiting. Although it has several mechanisms
of action, one of the ways in which it works is by blocking the
activity of a tumor protein called epidermal growth factor (EGFR).
Researchers are studying other EGFR inhibitors for the treatment
of non-small cell lung cancer, including erlotinib (Tarceva)
and the monoclonal antibody cetuximab (Erbitux).
Two innovative approaches being tested for lung cancer treatment
are vaccination and gene therapy.
Vaccination. The GVAX lung cancer
vaccine is made from a patient’s own tumor cells. These
cells are genetically modified to secrete a hormone that stimulates
the immune system to attack the tumor. In a study of 33 people
with advanced non-small cell lung cancer who received the vaccine,
3 (9%) went into complete remission that lasted about a year
and a half. Half the patients lived for at least a year, which
is longer than the six or seven months seen in other studies
with docetaxel. Two 75-person trials with the vaccine are currently
Gene therapy. Researchers at M.D.
Anderson Cancer Center and the University of Texas Southwestern
have identified three tumor-suppressor genes that reduce human
lung cancer growth in mice. They are hoping that by injecting
the genes into a patient’s lung tumor, cancer cells will
die or grow more slowly.
Lung Cancer Prevention
Taking a medication to reduce the risk of cancer is a relatively
new approach to cancer management. A number of agents are being
tested to see if they can reduce the risk of lung cancer in people
at high risk (mainly smokers and people who smoked for many years
9-cis-retinoic acid. In a 2003
study of 177 former smokers, 9-cis-retinoic acid repaired some
of the lung damage caused by smoking. This raises the possibility
that 9-cis-retinoic acid, a substance related to vitamin A, might
reduce the risk of lung cancer in former smokers.
Anethole dithiolethione (ADT). A
recent Canadian study looked at the use of ADT, a drug used to
treat dry mouth, in 101 current and former smokers with irregular
growths in their lungs. Compared with a placebo, ADT halved the
risk of developing new growths and progression of existing growths.
Cyclooxygenase inhibitors. A growing
body of evidence indicates that the cyclooxygenase-2 (COX-2)
enzyme plays a key role in lung cancer. Clinical trials are examining
whether drugs that inhibit this enzyme, for example celecoxib
(Celebrex), can reduce the risk of lung cancer in high-risk patients
or enhance the effectiveness of chemotherapy regimens.
Other agents. Hopkins researchers
are currently studying a drug called iloprost and a tea made
from broccoli sprout extract in people at high risk for lung
cancer, says Dr. Brahmer. To find out about more ongoing clinical
trials, visit www.clinicaltrials.gov (national)
or www.hopkinskimmelcancercenter.org (Hopkins