Mark A. Socinski, MD: Over 2 decades of research in clinical trials, examining the role that platinum-based chemotherapy plays in the treatment of this disease, have taken place in the past. The initial trials tested platinum-based chemotherapy versus best supportive care, or symptom management. They showed a survival advantage. The 1990s brought us 5 new drugs that are standard chemotherapy drugs—one of which was Taxol (paclitaxel), which became, kind of, the dominant player in combination with one of the platinums. After the turn of the century, another drug, pemetrexed, was developed and it had enhanced activity in nonsquamous, non–small cell lung cancer.
We did trials that looked at the number of chemotherapy drugs—1 versus 2, 2 are better than 1, 3 are not better than 2. So, we’ve done all of these clinical trials to get us to a platform where the standard of care, today, is a platinum. And we have 2 choices—carboplatin and cisplatin—and that’s typically paired with a second drug. The second drug does differ based upon what your histologic diagnosis is. Pemetrexed, as I mentioned, is for the adenocarcinoma subset. It is relatively less effective in squamous disease. In squamous, we typically have a choice of a taxane or gemcitabine paired with platinum. So that’s how we approach it and how we decide what the optimal 2-drug combination is. Again, it’s based on the underlying diagnosis being either squamous or nonsquamous, non–small cell.
Toxicities that patients worry about tend to revolve around nausea and vomiting. Acute chemotherapy got a bad reputation decades ago because we had relatively ineffective antinausea medications. That’s completely changed. Back in the 1980s, people would be hospitalized for a platinum-based therapy. Today, this is routinely given as an outpatient procedure, and patients go home and have very effective control of nausea and vomiting. So, in many ways, nausea and vomiting is no longer a major threat, from my point of view. Hair loss is a major concern to many people; that depends upon the type of chemotherapy you get. Drugs like Taxol and others do have a high likelihood of causing hair loss. We know that others—pemetrexed—have a low risk of causing hair loss. So there may be different options depending upon that.
Fatigue is a major problem with chemotherapy. That tends to be more cumulative in that it occurs the longer you’re getting chemotherapy, and that’s typically multifactorial. In each chemotherapy doublet, for instance, with the drug paclitaxel, you know there are unique side effects. It can cause neuropathy, numbness, tingling in your fingers, and that sort of thing. That is something we monitor for. Pemetrexed has a unique side effect of fatigue. It’s more likely to cause anemia than other things.
So, each drug has a slightly different side effect profile. And this is something that the patient, depending upon what the patient ends up getting treated with, should be somewhat familiar with—the common things that happen with those particular drugs so you can be informative with your symptoms and side effects. And that may allow supportive care to be much more customized to whatever issue you’re having with the chemotherapy. So that’s an important aspect from the patient’s point of view.