Major Trial of Four Newest Chemotherapy Regimens for Advanced NSCLC Shows Comparable Survival

MADISON, Wis—The first major trial to compare three of the newest chemotherapy regimens for advanced non–small-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 combinations—cisplatin (Platinol) and gemcitabine (Gemzar), cisplatin and docetaxel (Taxotere), and carboplatin (Paraplatin) and paclitaxel (Taxol)—were compared with a control combination of cisplatin plus paclitaxel.

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 Oncology’s 36th Annual Meeting.

Side Effects

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. Schiller reported.

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 “don’t 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.

Therapeutic Plateau

“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.