Select Excerpts from the Interview

Tracks 1-6

DR LOVE: What was your approach with this patient?

DR LILENBAUM: We enrolled her in the CALGB-30306 trial evaluating cisplatin/irinotecan in combination with bevacizumab as front-line therapy for extensive-stage SCLC. Two cooperative group Phase II trials were studying chemotherapy with bevacizumab in this population. The other was ECOG-E3501, evaluating cisplatin/etoposide with bevacizumab.

Both trials have since been completed, and preliminary data were presented at ASCO (Ready 2007; Sandler 2007). The reaction to the data was mixed, and some were disappointed with the ECOG results. I don’t believe they were bad — they just weren’t as good as we had expected.

DR LOVE: How did she tolerate the cisplatin/irinotecan/bevacizumab regimen?

DR LILENBAUM: She was able to complete six cycles and only encountered a mild hematological toxicity, which was compounded by the bevacizumab. I believe bevacizumab enhances the delivery of the chemotherapy to the bone marrow, so it’s more myelosuppressive.

Prior to therapy, the patient was coughing a lot, breathless upon minimal exertion and losing weight. While receiving treatment, she gained 10 to 15 pounds and all of her respiratory symptoms resolved. Within two cycles, she was back to baseline.

She had a near complete response. Imaging studies revealed only small hypodensities in the liver, and the disease in her chest was essentially gone. It was remarkable.

DR LOVE: Did you consider PCI at that point?

DR LILENBAUM: We talked about it, but she wasn’t enthusiastic about the idea of receiving radiation therapy to her brain. This is a problem we face with every patient when we discuss PCI. This patient had just completed six cycles of chemotherapy, so she was feeling good and wanted a break.

I did not push the issue because this was in 2006, and we didn’t have substantial data in extensive-disease SCLC at that time. So she did not receive PCI and within three months of completing chemotherapy, she developed brain metastases.

DR LOVE: If she presented today, would you be more inclined to recommend PCI?

DR LILENBAUM: Definitely. Based on the EORTC trial data, I believe that if this patient had received PCI, it may have been six months before she relapsed systemically (Slotman 2007; [1.1, page 4]). In the meantime, we would have prevented the development of CNS disease, which had an incredible impact not only on her outcome in general but also on her psyche.

DR LOVE: In your practice, what percent of your patients with small cell lung cancer respond to the extent that you could consider PCI?

DR LILENBAUM: With standard platinum/etoposide doublets, 15 to 25 percent of patients with extensive disease have a complete response and possibly another 15 to 25 percent experience good partial or near-complete responses. So anywhere from 25 to 50 percent of patients with extensive disease may qualify for this treatment.

DR LOVE: Of those patients who have a good response to chemotherapy, what percent relapse primarily in the brain?

DR LILENBAUM: According to the data, it can be as high as 25 percent for patients with limited-stage disease, and if the patient does not relapse systemically within six to 12 months, that number can reach almost 50 percent. I’m not sure it would be any different for patients with extensive disease (Aupérin 1999; Komaki 1981).

Tracks 7-10

DR LOVE: Can you comment on how you treated this patient and whether you tested the tumor for the presence of an EGFR mutation?

DR LILENBAUM: I did not test her tumor for a mutation. From a clinical research standpoint, I believe that information is important because it will help us design new trials and new drugs. However, in practice I don’t believe it’s necessary when deciding on therapy — with few exceptions.

We enrolled this patient on a Phase II trial of gemcitabine, oxaliplatin and bevacizumab. However, after two cycles we saw no response and she was more symptomatic. We stopped the chemotherapy and initiated single-agent erlotinib.

We started with 150 milligrams and within two weeks she had a Grade III rash on her face, scalp and upper chest in addition to oral mucositis, which I tend to see more often in elderly patients. We gradually tapered the dose to 75 milligrams, and she’s been on that for the past 18 months without progression of her disease.

The rash stabilized, as you see in the literature, within the first two to three months, as did the mucositis. Neither has been a problem for her since. Upon examination, you still see a few macular lesions and a little facial erythema, but she’s comfortable.

DR LOVE: What will be your approach if she develops disease progression?

DR LILENBAUM: I will probably administer a taxane or pemetrexed, and I’m tempted to continue the erlotinib. This is an unorthodox approach, but in the retrospective analyses of the TRIBUTE study, never smokers seemed to benefit from the combination of chemotherapy with erlotinib as opposed to chemotherapy alone and, anecdotally, I believe I see this in practice also (Herbst 2005).

Another option would be to add bevacizumab to the erlotinib when she progresses. I believe there’s a positive interaction with this combination, so it may be sufficient to stabilize her disease. However, if I chose this type of approach, I would probably add a cytotoxic agent and bevacizumab, and then after a while stop the cytotoxic agent, continuing just the erlotinib and bevacizumab.

Tracks 11-16

DR LOVE: Can you talk about your approach to this young woman?

DR LILENBAUM: When this patient presented with bone pain, imaging studies revealed disease in her femur and pelvis, and a biopsy was positive for squamous cell carcinoma. I was troubled by her presentation in the setting of this histology, so we biopsied the chest lesion and it revealed adenocarcinoma.

The staging studies then revealed liver lesions and extensive disease in the chest, so she received radiation therapy to the bone and then I treated her with cisplatin and docetaxel.

I told her that I believed it would be beneficial to add bevacizumab to that regimen but that there were risks for patients with squamous cell carcinoma, including pulmonary hemorrhage. She and her family asked questions and then she looked me in the eye and said, “I’m ready.”

She received five to six cycles of this regimen and had a nice partial response but still had measurable disease in her chest and liver. At that point, I decided that rather than waiting for a relapse, I would start her on erlotinib as soon as she finished her chemotherapy and keep her on bevacizumab also.

DR LOVE: Have you used this regimen before?

DR LILENBAUM: In similar cases, I have used all four drugs concurrently. This case required an intense thought process and, although I’m not sure exactly why, I felt that starting the erlotinib after finishing the chemotherapy was a better strategy. After she went on erlotinib and maintenance bevacizumab, she had a phenomenal response. Her PET scan three or four months later was negative in the chest, liver and bones.

DR LOVE: How did she tolerate the combination of erlotinib and bevacizumab?

DR LILENBAUM: She had no side effects from the bevacizumab. As for erlotinib, we started her on 150 milligrams, which was tough, so we reduced her to 75 milligrams. She’s been on this regimen for a year, and she’s comfortable and has almost no rash.

I know that some of my colleagues insist on keeping patients on higher doses of erlotinib, believing the rash will eventually improve. However, I feel that once you get them through the first two or three months, you should adjust the dose accordingly.

DR LOVE: How would you have treated her if she had presented with a Stage II tumor?

DR LILENBAUM: I would still have used cisplatin and docetaxel but not bevacizumab outside of a clinical trial. As for the erlotinib, I would discuss it with the patient after she completed her four cycles of adjuvant chemotherapy. This is a difficult position to be in because we’re not supposed to make decisions emotionally, but if it were me in that situation, I would want the drug.

Tracks 17-19

DR LOVE: How healthy did this 77-year-old man appear?

DR LILENBAUM: This patient was extremely fit. He had coronary heart disease, hypertension and diabetes mellitus, all under excellent control. He had a 30 pack-year history of smoking and had quit about 25 years before his diagnosis. He was focused on his health and was determined to do well.

He underwent a sleeve lobectomy and then we waited two months for him to recover before initiating adjuvant cisplatin/docetaxel, each at 75 mg/m2.

He completed three cycles with growth factor support and experienced no major complications. However, by the fourth cycle he was unhappy — which is the best word I can use to describe him — and asked if he could stop treatment.

I told him that in the clinical trials, the average number of cycles was three and that I wasn’t surprised that someone his age would want to stop then, even though his performance status was excellent. It’s been almost 15 months since his last cycle of chemotherapy, and he remains disease-free.

DR LOVE: Why did you use a combination of cisplatin and docetaxel?

DR LILENBAUM: In the adjuvant setting, I believe this is a more convenient regimen. It’s once every three weeks, and it’s only four cycles. In addition, I don’t recommend a port — rather, we’re able to complete four cycles with peripheral IV access.

In the Stage IV setting, we have evidence that this regimen is not inferior to cisplatin/vinorelbine (Fossella 2003), and I’m comfortable extrapolating that information to the adjuvant setting. I’m also comfortable with the routine prophylactic use of growth factors.

If you use cisplatin/vinorelbine, the patient will need a port and it requires weekly administration. I have used cisplatin/gemcitabine, but I haven’t incorporated that in my practice in the adjuvant setting. In patients for whom hair loss is a deal breaker in the adjuvant setting, I would feel comfortable with that combination.

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