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May 2012 Ask the Expert: Understanding Chemotherapy

During the month of May, Living Beyond Breast Cancer expert Jennie Lattimer, CRNP, answered your questions about chemotherapy for early-stage and metastatic breast cancer.

Standard chemotherapy for triple-negative breast cancer?

What is the current thinking regarding Taxol before versus after Adriamycin and Cytoxan (AC)?

Possible long-term adverse effects from pegfilgrastim (Neulasta) given with dose-dense chemotherapy?

When is chemotherapy recommended or not recommended for residual disease found at surgery when neoadjuvant chemo was given? When/if recommended, which chemo is recommended and how is that determined?

How does one decide between TAC (Taxotere, Adriamycin, Cytoxan) every three weeks for six cycles versus ACT (Adriamycin, Cytoxan, Taxol) dose dense: AC every two weeks for a total of four cycles then T every two weeks for a total of four cycles?

What are the risks of heart damage from doxorubicin (Adriamycin), and what to look for in regards to treatment?

After four sessions of Taxol, I developed neuropathy and went on docetaxel (Taxotere). Will this neuropathy go away?

I have heard that chemobrain lasts three years, but I am sure it is individualized. What can be done to clear your brain and body of toxins safely? I’ve also had several cases of deep vein thrombosis (DVT) and heard my vessels will never recover from all the damage.

Will my taste buds get back to normal?

Question: What is considered the standard chemotherapy for triple-negative breast cancer?

Ms. Lattimer: The standard therapy for triple-negative breast cancer (TNBC) is dose-dense doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) every two weeks for four cycles followed by dose-dense paclitaxel (Taxol) every two weeks for four cycles.

If you have a cardiac condition, undergoing treatment with an anthracycline such as doxorubicin would be inadvisable. If this is this case, you should discuss other options with your oncologist.

TNBC has also been linked to BRCA mutations. Researchers are studying platinum-based chemotherapies and PARP inhibitors, or poly ADP-ribosepolymerase inhibitors, in this population. PARP inhibitors block enzymes in cancer cells that help them repair damaged DNA. When cancer cells cannot repair DNA after treatment, they eventually shrink or die.

Question: A few years ago there was a poster session at the San Antonio Breast Cancer Symposium (SABCS) that said Taxol was better prior to Adriamycin and Cytoxan (AC) rather than after AC. What is the current thinking regarding Taxol before versus after AC?

Ms. Lattimer: Researchers are studying Taxol before Adriamycin and Cytoxan, however there is no data on this change of therapy yet. The standard of care is AC followed by Taxol. Depending upon your specific tumor, all three medicines may not be needed. It is important to discuss your individual treatment plan with your oncologist.

Question: What is known about possible long-term adverse effects from pegfilgrastim (Neulasta) that is given with dose-dense chemotherapy?

Ms. Lattimer: Neulasta has been on the market since 2002. The short-term side effects include bone pain, pain in the extremities and rare gastrointestinal upset. It usually lasts from five to 10 days. Some studies and retrospective studies look at the long-term risks. There are no specific long-term side effects to date.

Question: When is chemotherapy recommended or not recommended for residual disease found at surgery when neoadjuvant chemo was given? When/if recommended, which chemo is recommended and how is that determined?

Ms. Lattimer: The standard is no additional chemotherapy after neoadjuvant chemotherapy. You will complete trastuzumab (Herceptin) if your cancer is HER2 positive and/or endocrine therapy if your cancer is ER/PR positive. There have been studies looking at additional therapy, but none to date have shown an improvement in overall survival.

Question: How does one decide between TAC (Taxotere, Adriamycin, Cytoxan) every three weeks for six cycles versus ACT (Adriamycin, Cytoxan, Taxol) dose dense: AC every two weeks for a total of four cycles then T every two weeks for a total of four cycles?

Ms. Lattimer: This is a discussion you should have and a decision you should make with your oncologist. There has not been a head-to-head study looking at TAC (six cycles) vs. A/C followed by Taxol dose dense or every three weeks.

When the Cancer and Leukemia Group B (CALGB) performed a trial (9741), they looked at the following four groups:

  • A-T-C every three weeks for a total of four cycles
  • A-T-C every two weeks for a total of fourcycles
  • AC followed by paclitaxel (Taxol) every three weeks for four cycles each, and
  • AC followed by paclitaxel (Taxol) every two weeks for four cycles each. The women in the dose-dense arms received growth factor support with filgrastim (Neupogen) on days three through 10.

Researchers looked at whether the medicines should be given one after the other or at the same time. They found that after 36 months, women treated in the dose-dense groups (second and fourth bullet points) had a significantly higher disease-free survival, or length of time after treatment ends that a woman survives without any signs or symptoms of cancer,then those receiving standard dosing every three weeks (first and third bullet points). There was also a significant benefit in overall survival favoring the dose-dense study arms. The women in the dose-dense arms had more anemia-related events.

When oncologists started giving dose-dense AC followed by paclitaxel, they found that this was a very tolerable regimen. Women like this regimen because it is given over 16 weeks as opposed to 18 weeks.

Question: Doxorubicin (Adriamycin) was given to me to fight triple-negative breast cancer. I am praying that heart damage now and in the future will be minimal. What are the risks of this side effect, and what can I look for in regards to treatment?

Ms. Lattimer: Adriamycin has been used to fight breast cancer for more than 25 years. Anthracyclines are believed to cause immediate damage of the myocardialcells, specialized smooth muscle cells found in the myocardium, the muscular tissue of the heart, although it might be months or years for this damage to become clinically apparent.

We know that dose–related side effects develop over time. It is recommended that women receive no more than 550 mg/m2 in their lifetime. The dose that women receive during dose-dense therapy is 240 mg/m2. This is well below the maximum dose.

Risk factors for heart damage caused by anthracyclines include age (those over age 70 are at higher risk), the presence of other diseases such as hypertension and pre-existing coronary artery disease, sex (females are at higher risk) and previous cardiac irradiation or anthracycline chemotherapies.

Symptoms of heart damage caused by anthracyclines include shortness of breath, fatigue, and fluid retention such as swollen ankles. These are generally seen as symptoms of congestive heart failure.

Question: I have had four sessions of AC and then Taxol scheduled for 12 weekly sessions. After four sessions of Taxol, I developed neuropathy went on docetaxel (Taxotere). Will this neuropathy go away?

Ms. Lattimer: Taxol-induced peripheral neuropathy can be permanent. If significant neuropathy occurred early in your chemotherapy regimen, your symptoms may be permanent; unfortunately, only time will tell.

Switching therapies can help prevent permanent neuropathy. Typically, we will see more severe symptoms of neuropathy for a couple of months after treatment has stopped or been switched. It can peak a few months later, but then it usually gets gradually better over time. Medicines like gabapentin (Neurontin) and pregabalin (Lyrica) have been used to help with the symptoms of peripheral neuropathy, however they only mask symptoms, not treat them.

Question: I have heard that chemobrain lasts three years, but I am sure it is individualized. What can be done to clear your brain and body of toxins safely? I’ve also had several cases of deep vein thrombosis (DVT) and heard my vessels will never recover from all the damage.

Ms. Lattimer: “Chemo brain,” or cognitive changes due to chemotherapy, can occur. These changes include cognitive fatigue, short-term memory loss, difficulty focusing, decreased ability to multi-task and decreased reading comprehension.

Researchers know that the more chemotherapy treatments happen over time, the worse these changes can be. They also know that cognitive function does return, however each woman is different in how long it takes her to recover. It is possible that some cognitive changes can persist for up to two years, however cognitive changes persisting beyond three years should be examined further by your physician.

Some medicines that have been studied as potential treatments include methylphenidate (Ritalin) and dexmethylphenidate (Focalin) to help with concentration. I am not aware of any medicines or herbs that can clear your brain of toxins.

Once you have had a DVT, you are at greater risk of having recurrent blood clots.Your risk is highest within the first six to 12 months of the initial clot. The normal medical treatment is anticoagulation. The length of anticoagulation treatment is determined by different factors based upon your individual history. You should discuss your risk of recurrence for a blood clot with your doctor.

Question: Will my taste buds get back to normal?

Ms. Lattimer: Yes, your taste buds will return to normal. On average, women report that their taste returns in one month and as late as three to four months. A taste bud’s lifespan is approximately 10 days.

Denver, CO  ·  September 13, 2014

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