Rounds with the Investigators 2012 | Breast Cancer

DR NEIL LOVE: So Hal, this one we got, actually, from a colleague of Sara’s at UCLA, Dr Barstis, who apparently is a listener to our audio programs. He’s on the clinical faculty there?

DR SARA HURVITZ: Yes. He actually trained me once upon a time. He’s an excellent clinician. Yes.

DR LOVE: So Hal, he goes, “I was listening to your latest audio and I hear Cliff Hudis talk about using IV CMF as adjuvant therapy.” And he’s questioning that. He says, quote, “I still have a yellowed copy of an article by Goldhirsch in 1998 saying that IV adjuvant CMF doesn’t work.” And I guess there are not too many people who’ll come out publicly, like Cliff does, and say that’s what he does. But I actually also wanted you to address the editorial that you wrote — again, one of the many editorials — about trying to streamline adjuvant chemo choices.

DR HAROLD BURSTEIN: Yes. There’s actually been a lot of ongoing work with adjuvant chemotherapy. And that, I think, has actually clarified things a lot. So what we just saw at ASCO was data from NSABP-B-38, that compared dose-dense AC/paclitaxel versus AC/paclitaxel plus gemcitabine versus the 6-drug regimen of TAC. And in that study, adding gemcitabine was of no value. And in terms of efficacy, dose-dense ACT and TAC were essentially the same. There was a 2% difference numerically in disease-free survival favoring ACT. There was no difference in overall survival.

The side-effect profiles differed. TAC had a lot more neutropenia and febrile neutropenia and fatigue. And ACT had more neuropathy.

This comes on the heels of a variety of studies that have looked at adding 5-FU analogs or adding gemcitabine analog to anthracycline and taxane-based therapy. And none of them have shown any superiority.

We also know from previous work from ECOG in their 1199 trial that AC followed by paclitaxel was superior to AC followed by docetaxel. So actually I think for higher-risk patients with ER-positive or ER-negative disease, there’s no regimen that’s better than AC followed by paclitaxel. You can give the paclitaxel once a week or you can give it every 2 weeks. That is a gold standard that is perfectly reasonable and, to my eye, looks like the most well-tolerated regimen. I find it to be better tolerated than TAC. It’s shorter. It’s only 16 weeks of therapy as opposed to 18 weeks of therapy. You have to use growth-factor support either way.

So actually, I think for the vast majority of patients that’s a perfectly adequate chemotherapy regimen, representing the gold standard, based on cooperative group studies, the overview analysis and everything else we know.

Then if the tumor’s HER2-positive, you can just add the trastuzumab during the paclitaxel phase of therapy.

Now for women who don’t want to get anthracyclines, if the tumor’s HER2-negative, you have options such as docetaxel/cyclophosphamide or TC, and you have other options going back a generation, such as CMF. And for those women whose tumors are HER2-positive and you don’t want to give an anthracycline, you obviously have the TCH data to call upon. So I think you only need a very small repertoire of regimens right now.

DR LOVE: “So, Doctor, I went to this doctor at Memorial Sloan-Kettering called Dr Hudis and he suggested I get IV CMF. Is that okay or should I not do it?”

DR BURSTEIN: Well, talking to Cliff Hudis about adjuvant chemotherapy is like talking to Ted Williams about how to hit a baseball. They know what they’re talking about. So you never want to be on the opposite side of that discussion.

We actually pulled all the numbers in the NCCN registry recently, and there were 21 different adjuvant regimens used to treat breast cancer at the NCCN institutions. And they included CMF. To my mind, it’s hard to really know who needs CMF. I guess it would be the patient who doesn’t want an anthracycline and who doesn’t want 4 cycles of TC, which is a reasonably well tolerated, reasonably short regimen at 12 weeks.

There’s not a lot of data for IV CMF. Most of the studies in the literature that looked at CMF, and the Italian group in Milan, which has classico CMF, were all built around oral cyclophosphamide dosing, 2 weeks on, 2 weeks off for 6 months. That’s a tough regimen. IV CMF emerged as being more fashionable because it was easier. It’s usually 6 cycles once every 3 weeks. It often does not make your hair fall out. Whether it really is adequate chemotherapy, I think if you’re talking about a relatively low-risk tumor with ER-positive features, sure, [it] probably doesn’t make that much difference. But it’s not a regimen that we actually use very much.