Chapter 21: Drug Treatments and Multi-disciplinary Treatments for Sarcoma; A View on the Moon Shots Program

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Chapter 21: Drug Treatments and Multi-disciplinary Treatments for Sarcoma; A View on the Moon Shots Program

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In this chapter, Dr. Benjamin talks about his research focus on sarcoma treatments, neoadjuvant therapy, and the treatment of metastatic disease. Next, he talks about collaborations resulting in multi-disciplinary treatments. He notes that as the Division of Medicine was divided into disease groups, it was easier to build collaborations. Dr. Benjamin describes results achieved by treating bone tumors with intra-arterial Cisplatin. He describes the "one of the most amazing results" that saved a patient from having a hemi-pelvectomy. With such successes, Dr. Benjamin says, it was easy to convince surgeons of the benefits of collaboration. He also notes that multi-disciplinary treatments were aided by advances in imaging. Finally, Dr. Benjamin offers some comments on the Moon Shots Program.

Identifier

BenjaminR_02_20150116_C21

Publication Date

1-16-2015

City

Houston, Texas

Topics Covered

The Interview Subject's Story - The Researcher; The Researcher; Overview; Definitions, Explanations, Translations; Discovery and Success; Multi-disciplinary Approaches

Transcript

Tacey Ann Rosolowski, PhD:

(laughs) I’m looking at the list of some of the other things that you worked on, and these I kind of just gleaned from background research that Javier at the Archives sent me. So I can go through this or you could tell me what you recall as being kind of the next significant thing you worked on after the toxicity studies.

Robert Benjamin, MD:

So I think after the anthracycline studies and the cardiac toxicity, my focus got more and more on sarcomas, and we continued to study a number of new drugs in the treatment of sarcomas, usually with very little success after the initial Adriamycin-based combinations. The initial therapies really all came from Jeff Gottlieb, minor modifications within them, so our standard regimen for soft-tissue sarcomas was either ADIC, Adriamycin and Dacarbazine, that used to be known as DIC and is commercially now called DTIC, but ADIC or CYADIC, adding Cyclophosphamide to that regimen, and that became the backbone of our sarcoma chemotherapy. We used those regimens for soft-tissue sarcomas with the multidisciplinary interaction with surgery, so often doing both chemotherapy and surgery for patients, even with metastatic disease.

Tacey Ann Rosolowski, PhD:

Were these chemos that were given prior to surgery?

Robert Benjamin, MD:

Yes. Often even in patients with metastatic disease, because for soft-tissue sarcomas, for the majority of soft-tissue sarcomas, like osteosarcoma, the lung is the primary target organ and they don’t tend to spread everywhere in the body. So, often if you could limit the number of pulmonary metastases and the growth rate of the pulmonary metastases, you could add on surgery to remove those and help to demonstrate that patients could actually live sometimes for a very long time after removal of metastatic disease.

Tacey Ann Rosolowski, PhD:

I was just curious. I mean, I’m sorry if I’m derailing you. But suddenly we’re involving surgeons in this as well, and I’m curious, like, was there a process by which you were able to identify the surgeons who were interested in taking part in those multidisciplinary treatments? You know, what was that all about?

Robert Benjamin, MD:

So as the Developmental Therapeutics era ended and medicine became much more subdivided into disease groups, it was actually much easier to get some of the interdisciplinary interactions, because the surgeons who dealt with sarcomas knew the medical oncologists who dealt with sarcomas, and we all found that we needed each other’s help. So multidisciplinary therapy basically is based on the fact that no one group is usually successful in treating these patients. So the surgeons would find that, you know, they would do all of their therapy on their patients only to find that the majority of them would wind up with pulmonary metastases. We would find that even if we got a good response to chemotherapy, we could rarely get everything to go away, and we needed to enlist the aid of the thoracic surgeons, who sometimes took some of these out by themselves. So we were just able to get better interdisciplinary therapy going.And I think part of the interdisciplinary therapy occurred when the surgeons sent us some patients with sort of extreme problems with localized disease, and they just didn’t know what to do, so they sent them on to Medicine. Every once in a while, we would treat them and get a good result and have them go back to the surgeon and say, “Well, now can you do something?” I mean, there were a few patients who really tilted the balance in that sort of therapy.When we started using intra-arterial Cisplatin, we got some profound local effects, especially with primary bone tumors. So there was one patient who had come to us who had a tumor of her pelvis, of her pubic bone, and she’d been treated outside with radiation and some chemotherapy, and was getting worse, came here, and went to the surgeons for radical surgical treatment. And the surgeons said, “We can’t do a hemipelvectomy on this woman because her tumor is too extensive and we won’t be able to get around it.” So they sent her to us, and we treated her with intra-arterial Cisplatin, and she had one of the most dramatic responses I’ve ever seen. It’s a story I don’t forget, because we treated her with intra-arterial platinum and had her go back home, and she was set to come back in three weeks for another treatment. About a week and a half after she got her treatment, she called up and said, “I have a new mass. I’m coming back.” And I tried to explain to her that it didn’t help her to come back because I couldn’t treat her yet until she recovered from the toxicity of the previous therapy, but she was somewhat anxious, so she appeared on our doorstep the next day.The new mass that she had was her iliac crest, that she hadn’t been able to feel for months because she had so much edema around it from her tumor, and the tumor had, with one treatment, shrunk more than in half, and with a couple more treatments basically disappeared, except for whatever was left in the bone.So I sent her back to the surgeon and said, “Do you think you can cut this out now?”And he said, “Well, yeah, I think I can cut this out, and I don’t even think I have to do a hemipelvectomy. I can just remove her pubis anteriorally, and we should be able to get around this whole tumor.” So he cut out the bone, and the pathologist couldn’t find any tumor in it.So the surgeons thought that was something that we did all the time, and we tried not to discourage that misconception. So we started being able to interact with them, where we would try on patients with primary tumors to treat them preoperatively with chemotherapy and then do surgery. So it was relatively easy to convince the surgeons who dealt with bone tumors to do that, and the therapy for bone tumors was better.But we also eventually got the surgeons dealing with soft-tissue sarcomas to also accept the concept of neoadjuvant chemotherapy. We’d been doing that here for quite a long time, and as the systemic therapy improves, the likelihood of benefit from the multidisciplinary therapy improves. And, of course, it’s all been aided by advances in imaging, where we can actually see what we’re doing now much better than we could in the past. So we slowly developed multidisciplinary approaches that occasionally result in better-than-expected outcomes. And, again, this is not something that we achieve all the time or even most of the time, but the fact that we can achieve it sometime is remarkable compared with where we were before.

Tacey Ann Rosolowski, PhD:

This is kind of a side question, not doing the chronology of your research, but just the way you framed that statement, “It’s not something we can achieve all the time, but we can achieve it sometime,” that just kind of—

Robert Benjamin, MD:

And part of that goes back to Dr. Freireich’s approach, which is if you don’t try, you never succeed.

Tacey Ann Rosolowski, PhD:

I’m wondering, too, how it—you know, working from that perspective, what is your view of, like, the Moon Shots program and the whole low-hanging fruit? I value your commentary on that.

Robert Benjamin, MD:

Um—

Tacey Ann Rosolowski, PhD:

We can also turn off the recorder briefly, if you’d like. (laughter)

Robert Benjamin, MD:

I think the basic concept is a good one. I think the low-hanging fruit is more likely to be bird-pecked.

Tacey Ann Rosolowski, PhD:

(laughs) And what do you mean by that?

Robert Benjamin, MD:

So, I mean, I think that some of the approaches, although highly sophisticated in terms of what’s being done, are relatively simplistic in terms of the concept that if you just take care of this area of low-hanging fruit, we will address the problem. I think the cancers maybe a lot smarter than that. But I’m not the right person to judge that sort of an issue. I mean, I don’t have sufficient detailed knowledge in the areas where the particular studies are being done to be able to say whether they will or won’t succeed. I think they’re for sure worth exploring. I think they may be more effective in some areas than in others.

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Chapter 21: Drug Treatments and Multi-disciplinary Treatments for Sarcoma; A View on the Moon Shots Program

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