Dr Love: Andy, you said you would start this patient on a taxane — which agent would you choose?

Dr Seidman: Presently, we don’t have evidence to make this decision, but I understand in the not too distant future we will have some prospective randomized comparisons between paclitaxel and docetaxel. Right now, I can’t give you the evidence-based answer.

Sometimes the symptom of shortness of breath helps me choose between the taxanes. Docetaxel in cumulative doses that exceed 400 to 600 milligrams per meter squared can sometimes lead to a syndrome of fluid retention, including pleural effusion. We started seeing this back in the early 1990s, and the use of corticosteroid premedication has made it much less common. But, in this scenario, I would favor paclitaxel because it would be less likely to confound my assessment of her primary symptom of shortness of breath.

Dr Firstenberg: In general, in a patient who is taxane-naïve, is there any data to suggest whether it’s better to use paclitaxel followed by docetaxel, or the opposite?

Dr Seidman: Is one taxane more active after the other in terms of cross-resistance? I don’t think we know that. But we also don’t necessarily know that answer for steroidal and nonsteroidal aromatase inhibitors, for which there has been a lack of cross-resistance. I wouldn’t select an agent based on that notion.

Dr Love: What would you do if she had a dramatic response to paclitaxel and was doing great after two or three cycles?

Dr Seidman: What is the optimal duration of therapy? Do you treat for some arbitrary number of cycles, stop and observe? Do you treat to the maximum response as assessed by CT scan and stop? Do you treat to the maximum response as assessed by CT scan and then add a few extra cycles? Or do you treat until disease progression, as long as there’s no intolerable toxicity? I tend to do the latter.

The natural history of metastatic breast cancer is to grow, progress and cause death. If I’ve changed that natural history, as long as the treatment is reasonably well-tolerated, my bias is to continue. However, if this woman had, as Dr Wilson presented, estrogen receptor-positive disease, I have the option of backing off and using second-line anti-estrogen therapy.

Dr Love: What schedule of paclitaxel would you use?

Dr Seidman: I am the principal investigator of CALGB-9840, which randomizes patients to weekly dose-dense or conventional paclitaxel every three weeks. We don’t yet know the right answer. Until we do, the practical, logistic issues influence me.

It’s not a major issue for my patients living on East 79th Street to come in for weekly therapy. Weekly therapy, however, for my patients commuting from New Jersey, Connecticut, or Long Island, could be inconvenient, especially in the absence of any randomized Phase III data showing benefit.

Dr Love: For ER-positive disease, you mentioned the strategy of giving chemotherapy to induce response and stabilize the patient and then switching to a hormonal therapy. Let’s say this patient has been treated for four months and is having a good response but with some neurotoxicity. Is that something you would be likely to do?

Dr Seidman: Absolutely. I think the best thing we can do for patients with potentially hormone-sensitive breast cancer is to give them antiestrogen therapy. The only thing in this scenario that pushed me to cytotoxic chemotherapy was the more symptomatic, aggressive profile you illustrated. I would welcome the first opportunity to back off of chemotherapy and to start an aromatase inhibitor.

Dr Love: Now, for example, let’s make this woman HER2-positive by FISH, with lymphangitic disease and severe shortness of breath. Debu, how would you treat her?

Dr Tripathy: I would certainly use trastuzumab therapy in this situation. We know that it improves the response rate, quality of life, duration of response and survival when used in combination with chemotherapy compared to chemotherapy alone.

The question is what trastuzumab-containing regimen to use. The comparative trials are with paclitaxel/trastuzumab, and this would be the standard and my initial choice. However, with recent data suggesting that higher response rates can be achieved with the addition of carboplatin, this would be an important option to discuss with the patient.

I wouldn’t offer the triplet in a knee-jerk way, but I probably would use it. There is not that much more toxicity, but there is more fatigue and more severe cytopenias. In this particular case, I probably would consider the triplet therapy with trastuzumab, carboplatin and paclitaxel.

Dr Love: Ok, now you put her on the triplet and after three months of therapy she’s having a good response and doing well. What would you do at that point?

Dr Tripathy: As soon as her disease has plateaued and I felt additional therapy would not result in much further benefit, I would stop the chemotherapy and continue trastuzumab alone. The point at which that plateau is reached varies with each patient, the symptomatology and the tolerability of therapy. In the published trial, patients needed to receive at least six cycles before having their treatment discontinued. The vast majority did discontinue chemotherapy around that time or shortly thereafter.

Case follow-up:
•	Patient received docetaxel (75 mg/m2) q 3 weeks; tolerated chemotherapy well with symptomatic improvement
•	CT scan after the third cycle indicated a response; additional 3 cycles were given

Dr Love: Let’s follow up with Dr Wilson and find out exactly what happened.

Dr Wilson: She agreed to receive six cycles of docetaxel at 75 mg/m2 every three weeks. She tolerated therapy well with symptomatic improvement, and her CT scan after the third cycle showed some response.

Dr Seidman: Dr Wilson, I’m just wondering why you chose a dose of docetaxel of 75 mg/m2? Were you concerned about the impact of 100 mg/m2 on her quality of life?

Dr Wilson: Yes, I was concerned about that. There was a question of giving her hormonal therapy up front. Since she had visceral metastases and symptoms, I wanted to give her chemotherapy, but she was working. She wanted to be treated, but she also wanted to minimize toxicity. I thought it was reasonable to give docetaxel at that dose and monitor her response.

Dr Seidman: One of the questions posed to me was which taxane would I use. The randomized data comparing these two taxanes compares docetaxel at 100 mg/m2 to paclitaxel at 175 mg/m2.

We also have randomized Phase III data on docetaxel dosing, comparing 100 to 75 to 60 mg/m2, indicating a higher response rate and longer time to progression with the higher dose (Table 4). It’s interesting that some of my colleagues in the community still aren’t comfortable with the 100 mg/m2 dose, despite its positive impact on quality of life.

Dr Tripathy: This issue is critical. Whereas with paclitaxel there doesn’t seem to be much of a dose-response relationship increasing from 175 to 225 to 250 mg/m2, with docetaxel, it does matter. And the toxicities are clearly different at 75 versus 100 mg/m2.

Dr Cohen: I generally have used 75 mg/m2 of docetaxel, because there’s less of an issue with fluid retention and also fatigue. Isn’t it true that a significant number of patients in many of the studies start at 100 mg/m2 and have to decrease to 75 mg/m2 because of toxicity?

Dr Tripathy: Yes, so the dose delivered may actually be lower than 100 mg/m2, but in an intent-to-treat analysis, this is generally presented as the 100 mg/m2 dose. One can extrapolate to say: We can probably just start at 75 mg/m2. While it is very hard to say, I believe the answer might be somewhere in between.

Case follow-up:
•	CT scan indicated stable disease
•	Patient switched to anastrozole as maintenance therapy
•	Remained on anastrozole, working and feeling well for 7-8 months

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