American Association for Cancer Research

Clinical Trials and Special Patient Populations

Location, location, location: U.S. versus Japan—same drug, unexpectedly different outcomes

Let’s look at some more examples. We use a drug called Taxotere to treat breast cancer and lung cancer. In the United States, the dose we use is 100 mg/m2—so it’s based on your body’s surface area. Sometimes we use 75 mg/m2. In Japan, doctors use 60 mg/m2. Japanese researchers did the same studies that we did before deciding on a dosage. The thought here was that maybe the Japanese researchers did not do their studies properly, or that maybe they were so concerned about side effects that they stopped treatment at any little sign of side effects.

Recently, however, a cooperative group called the Southwestern Oncology Group was doing a study in lung cancer—a phase III trial comparing different treatments. One of the treatments involved the chemotherapy drugs paclitaxel and carboplatin. And there was a Japanese study that also was using paclitaxel and carboplatin. Patients in the two studies in the United States and Japan were treated the same way. The only difference was that in Japan the dose of paclitaxel was lower than in the United States. With chemotherapy drugs, the more you give the more side effects patients have. So the expectation was that the side effects would be less in Japan than in the United States. In addition, we would also predict that the results may not be as good in Japan because we think that the higher the dose of chemo, the better the results.

We were all wrong.

First, look at the side effects. In this study, 69 percent of the folks in Japan had grade IV neutropenia, meaning that their white blood cells were almost completely wiped out. This compared with 26 percent in the United States, even though Japanese doctors gave the lower dose of chemotherapy. And, if you looked at those who got the neutropenia and had a fever and so on, it was 18 percent in Japan compared to 3 percent in the United States. Of those who had anemia, it was 15 percent in Japan compared to 6.5 percent in the United States.

Then, look at how the patients did. In the Japanese study, about half of the folks were alive in one year. In the U.S. study it was just 37 percent—even though in Japan, the researchers used the smaller chemotherapy dose.

In this clinical trial, the outcome was actually different for patients in the two countries. In Japan, they had more side effects and they had a better outcome, even though the patients received a lower dose of the drug. We have some insights into why this may happen and we’ll talk about that later.