FAQs about Chemotherapy

I have received a recommendation for "TAC" chemotherapy. Is that the best I can receive? 

TAC is just one of many acceptable regimens. For patients who are in a "high-risk" category for breast cancer, we like to use aggressive chemotherapy regimens that would be more effective in increasing the cure rate. TAC (Taxotere^® [docetaxel], Adriamycin^® [doxorubicin], and cyclophosphamide) is one such regimen that has been shown to improve survival of patients who have undergone surgery for breast cancer involving lymph nodes in the armpit.

There is, however, reason to believe that women with large tumors, high-risk features, and no involvement of the lymph nodes could benefit from aggressive therapy. There are other treatments containing doxorubicin and docetaxel or Taxol^® (paclitaxel) that are used in such women. However, there are subtle differences in the effectiveness of these treatments, their schedules of delivery, and side effects. Your oncologist is the best judge of the right treatment for you.

Can I receive TAC with Herceptin^® (trastuzumab)? 

The use of trastuzumab cut the risk of breast cancer returning after initial treatment by half in four large randomized trials. These trials compared chemotherapy with trastuzumab versus chemotherapy alone. Some of these studies used trastuzumab at the same time as chemotherapy, whereas one very large trial conducted outside of the United States used trastuzumab only after completing all chemotherapy.

Since the TAC (Taxotere^®, Adriamycin^®, and cyclophosphamide) regimen contains Adriamycin (doxorubicin), which substantially increases the risk of heart damage when given at the same time with trastuzumab, the only way to deliver trastuzumab with TAC would be to finish TAC first and then start trastuzumab. Looking at the results of the trial outside the United States (HERA trial), one could easily justify doing that.

However, different ways of administering trastuzumab were employed in U.S. studies in which AC (Adriamycin and cyclophosphamide) treatment was delivered before initiating trastuzumab concurrently with Taxol^® (paclitaxel)—given every 3 weeks or weekly, or Taxotere (docetaxel)—given every 3 weeks. One of the studies used Paraplatin^® (carboplatin) and docetaxel with trastuzumab, and avoided doxorubicin all together. So in summary, yes, you can receive trastuzumab after finishing six cycles of TAC, but you should talk to your oncologist who understands your circumstances the best and can individualize your treatment after explaining the pros and cons of these options.

I have heard that TAC is a very toxic treatment. Is that true?

Everybody's reaction to chemotherapy is different. TAC is well tolerated by most patients. Some patients, however, may have side effects, such as severe drop in the white blood cell count or occasionally a fever. It can also cause some nail changes, fatigue, and fluid retention. There is of course hair loss, which is universally seen with this and other Adriamycin^® (doxorubicin)-combining regimens.

The most common and worrisome side effect of TAC is the severe decline in white count and rising fever in up to one-fourth of patients. This has now been shown to be diminished by use of growth factors, such as Neupogen^® (filgrastim) or Neulasta^® (pegfilgrastim). Every patient receiving TAC should now be given either pegfilgrastim, which is a single injection given the day after chemotherapy with its effects lasting about 2 weeks or so, or filgrastim once a day for 10 days. These growth factors decrease the risk of a dangerous drop in white count and fever to low single digits (3 percent to 5 percent).

Can you tell me about the injection I have to receive to "boost" my immune system?

What you are referring to is either Neupogen^® (filgrastim), Neulasta^® (pegfilgrastim), or Leukine^® (sargramostim), which are injections given to make your bone marrow recover faster and bring up your white cell count. White cells fight infection in your body and their amount goes down about 5 to 7 days after chemotherapy. It takes another 7 to 10 days to recover. By giving these injections, we make the duration of recovery much shorter and the reduction of white cell count much less. This has an effect on preventing severe infections.

Dose Dense (DD) 

What is the advantage of dose-dense therapy? Is there a downside? 

Breaks between chemotherapy doses are meant to give a chance for normal cells of the body, particularly bone marrow, to recover. There is a concern that cancer cells keep growing during those "recovery breaks," which are ordinarily 3 to 4 weeks long.

Dose-dense therapy is a way to give chemotherapy every 2 weeks instead of every 3 weeks by injecting drugs, such as Neupogen^® (filgrastim) or Neulasta^® (pegfilgrastim), to bring your white count up faster to enable you to receive the next cycle of chemotherapy sooner. The theoretical advantage of dose-dense therapy is to not allow a 3-week drug "holiday" for cancer cells to repopulate.

This approach, when compared with an every 3-week approach of chemotherapy delivery, showed a slight advantage in survival rates after 5 years. The other advantage is that the patients finish chemotherapy in 4 months instead of 6 months.

There is very little downside to this therapy in terms of having to receive these injections to bring up your blood cell counts faster. In the original study, 13 percent of patients had to receive a blood transfusion. This is unlikely to be the case because of widespread use of red cell growth factors. The routine growth factor use, however, does make this therapy more expensive. It should also be pointed out that growth factors can produce side effects in some patients.

Can I receive dose dense regimen with Herceptin^® (trastuzumab)?

Although none of the large randomized trials of trastuzumab in early breast cancer employed the dose-dense regimen, there has been some limited experience showing its feasibility. I should caution that the first part of dose-dense therapy employing AC (Adriamycin^® [doxorubicin] and cyclophosphamide) should not be given concurrently with trastuzumab.

However, during the dose-dense Taxol^® (paclitaxel) part of that treatment, trastuzumab was combined with chemotherapy. The only difference in this approach is that the first dose of paclitaxel is being given only 2 weeks after the last dose of AC in this regimen as opposed to a 3-week gap in the larger experience of other research groups. You should discuss this with your doctor, who should be knowledgeable about these clinical trials and these warnings.

How many patients need Neulasta^® to boost their counts with the dose-dense regimen?

The original study of dose-dense regimen was conducted with every patient receiving Neupogen^® (filgrastim). Neulasta (pegfilgrastim) is the longer-acting version of that medicine and is now currently used with the dose-dense regimen. However, many physicians have observed that the same level of growth factor support may not be necessary during the Taxol^® (paclitaxel) part of this treatment and they tend to lower their use of growth factors during this phase of treatment. If you are experiencing bone pain during your Neupogen or Neulasta injections and notice that your white count is overshooting, you should discuss this with your physician to consider lowering the total dose of the growth factor.

My treatment with Taxol^® (paclitaxel) takes almost 4 hours. I have learned there is a new "Taxol" that can be given over a shorter time period. What do you know about that?

Paclitaxel by itself is an insoluble drug. To make it water-soluble, it is mixed with a castor-oil derivative, Cremophor^® EL. This solvent can cause allergic reactions, may damage nerves and blood cells, and may entrap some paclitaxel, interfering with its delivery to the tumor.

To prevent an allergic reaction and decrease side effects, several medications, such as steroids and antihistamines are given before paclitaxel and the infusion time is prolonged to about 3 hours. The "new" Taxol that you are referring to has been available since January 2005 under the name Abraxane^® (nanoparticle albumin-bound [NAB] paclitaxel) and employs a new way of making this drug soluble by enclosing it in microscopic particles of a natural protein called albumin.

This eliminates the need for Cremophor and avoids the problems listed above. NAB paclitaxel can be given over 30 minutes without any premedications to prevent an allergic reaction. In a randomized study, NAB paclitaxel resulted in a larger interval to cancer progression compared with paclitaxel as well as a higher response rate.

I have diabetes and my blood sugar goes up when I take my Decadron. Is there a way to avoid Decadron?

I believe you are referring to your Decadron^® (dexamethasone) use before your Taxol^® (paclitaxel) or Taxotere^® (docetaxel). The general trend has been to decrease the amount of Decadron before these chemotherapeutic agents, although the physicians are largely doing that empirically without any systematic study of the optimal dose of Decadron.

However, there is a new taxane, which is called Abraxane^® (nanoparticle albumin-bound [NAB] paclitaxel). This new type of paclitaxel does not require any Decadron use before its administration. You should discuss it with your doctor to see if you are a suitable candidate for switching to NAB paclitaxel.

Is Abraxane^® (nanoparticle albumin-bound [NAB] paclitaxel) as good as Taxotere^® (docetaxel)?

Answer: NAB paclitaxel has been compared to docetaxel in a recent randomized phase II trial. The weekly schedule of NAB paclitaxel has been shown to be more efficacious compared with every 3 weeks for docetaxel. A pivotal phase 3 trial comparing NAB paclitaxel weekly to every 3 weeks for docetaxel is planned. However, both agents have been compared with Taxol^® (paclitaxel) in separate randomized studies. In the trial where NAB paclitaxel was compared with paclitaxel, NAB paclitaxel could be given in a higher dose (260 mg versus 175 mg/m²), which resulted in more shrinkage of tumors and longer time to progression. Although toxicity to nerves was observed more frequently with NAB paclitaxel, it was shorter lived. This was believed to be due to the lack of the toxic solvent Cremophor (castor oil), which is used with paclitaxel to make it soluble.

A separate trial comparing docetaxel with paclitaxel showed docetaxel was better for shrinking tumors, time to progression, and overall survival at the cost of more suppression of bone marrow, more fevers, nausea, fluid retention, fatigue, and nerve damage. The dose of docetaxel used in the study was high, and it was given for eight cycles, something that is generally not done in most practices. Your oncologist is in the best position to choose your therapy after a discussion of the pros and cons with you.

Can Abraxane^® (nanoparticle albumin-bound [NAB] paclitaxel) be given instead of Taxol^® (paclitaxel) in the postoperative treatment of cancer?

Although there is no large experience of substituting NAB paclitaxel for paclitaxel in this setting, there are now pilot data beginning to emerge showing that this approach may be feasible. You should discuss it in more detail with your oncologist. All new drugs go through this phase of testing before there can be widespread endorsement for their use.

Is it true that I receive a higher dose of Taxol^® (paclitaxel) if I receive Abraxane^® (nanoparticle albumin-bound [NAB] paclitaxel)?

It is true that a higher dose of NAB paclitaxel was compared with the standard dose of paclitaxel in a clinical trial that showed the superiority of NAB paclitaxel in terms of likelihood of shrinking the tumors and time to disease progression. This higher dose is possible because NAB paclitaxel is not dissolved in Cremophor.

Cremophor produces side effects, such as allergic reaction, potential for nerve damage, and potential for entrapping the drug thus impairing its delivery to the tumor. NAB paclitaxel, on the other hand, binds paclitaxel to albumin, a natural protein, making it soluble. This enables a much shorter delivery time compared with traditional paclitaxel (one-half hour instead of 3 hours) and avoids the multiple medications given with paclitaxel to prevent an allergic reaction to Cremophor. This also enables a higher dose of paclitaxel to be delivered in the NAB paclitaxel formulation, which perhaps results in better efficacy of the drug.

Anthracycline 

My doctor wants to give me Ellence^® (epirubicin) instead of Adriamycin^® (doxorubicin) because he believes it will be less damaging to my heart. Is that true?

It is widely believed on the basis of clinical trials that milligram for milligram epirubicin has a lower potential for heart damage compared with doxorubicin. Epirubicin is widely used for the treatment of breast cancer, although it is more popular in Europe and Canada.  My doctor has prescribed Ellence^® (epirubicin) followed by Taxol^® (paclitaxel) as my treatment. Is that considered standard?

It is at least a standard. There are many different chemotherapies chosen by oncologists for use in the treatment of breast cancer, but there is no single therapy that can be considered the standard. Your oncologist has perhaps chosen it because of his or her belief that it is going to be less damaging to your heart. There is evidence that milligram for milligram epirubicin causes less damage to the heart compared with doxorubicin. There is, however, some debate about the optimal usage of both epirubicin and doxorubicin.