MADISON, WisThe first major trial to compare three of the
newest chemotherapy regimens for advanced nonsmall-cell lung
cancer (NSCLC) with the most commonly used combination found that all
offered similar survival benefits.
The phase III trial randomized the chemotherapy regimens, which are
in widespread use, among 1,146 patients with advanced lung cancer who
had not received previous treatment. Three combinationscisplatin
(Platinol) and gemcitabine (Gemzar), cisplatin and docetaxel
(Taxotere), and carboplatin (Paraplatin) and paclitaxel
(Taxol)were compared with a control combination of cisplatin
Among all four treatment groups, median survival was 7.8 months, said
Joan Schiller, MD, of the University of Wisconsin, lead author for
the Eastern Cooperative Oncology Group study. Gemcitabine/cisplatin
slowed the time it took cancer to recur to 4.5 months, compared with
3.5 months for the other treatments.
Although none of the four different arms turned out to be
superior, these results show that the chemotherapies tested in the
study improve survival, compared to historical controls, Dr.
Schiller said, referring to combinations and protocols in use 5 years
ago. Dr. Schiller spoke at the American Society of Clinical
Oncologys 36th Annual Meeting.
Slight differences in reaction to the drug occurred, but none had a
measurable effect on survival rate. The most commonly used drug
combination today, carbo-platin/paclitaxel, caused significantly
fewer side effects, such as nausea, vomiting, and fatigue, but also
demonstrated a lower response rate than the other drugs tested, Dr.
Grade 4 thrombocytopenia was more common with cisplatin/ gemcitabine.
Fever and neutropenia were less frequent among those receiving
cisplatin/gemcitabine, and those in the paclitaxel/ carboplatin
group. Nausea was least common among patients receiving paclitaxel/carboplatin.
These differences suggest the decision to use one regimen over
another should be based on weighing different parameters, such as
side effects, cost, dosing schedules, and response rate, Dr. Schiller said.
The next step in research will be to combine chemotherapy with
biologic drugs, such as angiogenesis inhibitors. We have lots
going on along these lines, she said, referring to phase I
studies of several combinations.
Although the current drug treatments still dont work very
well, Dr. Schiller said, combining them with drugs that have
completely different mechanisms of action may create synergy, thereby
increasing efficacy and reducing drug resistance.
A Challenging Disease
In general, NSCLC is a very difficult cancer to treat,
said Benjamin Movsas, MD, director of thoracic radiotherapy, Fox
Chase Cancer Center.
This important randomized study, however, shows that small, but
real, incremental improvements in outcome are occurring, even in
patients with metastatic disease. Since the four regimens
tested had similar efficacy, quality of life becomes a critical issue
in choosing a particular regimen, he said.
We appear to be approaching a therapeutic plateau with various
chemotherapy combinations in stage IV disease, Dr. Movsas said.
Fortunately, there are a multitude of novel biologic agents on
the horizon that are in the process of being studied.
Patients with NSCLC often present with metastatic disease, as in this
study, Dr. Movsas said. For this reason, he noted, efforts are under
way to detect NSCLC before it reaches such an advanced stage. One
possibility under investigation is screening with low-dose spiral CT imaging.