Rationale For Neoadjuvant Therapy As A Standard Of Care For Patients With Triple
Notably, two randomized neoadjuvant trials of PD-L1 antibodies, NeoTRIPaPDL1 which tested atezolizumab and chemotherapy and GeparNuevo which tested durvalumab and chemotherapy in TNBC, did not show increase in pCR with addition of this PD-L1 antibody compared to placebo. The GeparNuevo trial did show a significant increase in pCR in a subset of patients who received a window of 2 weeks of durvalumab before beginning chemotherapy .
A further rationale for NAC for TNBC is that subsequent adjuvant therapy can be implemented with the goal of improving outcomes for patients who lack a pCR result. The CREATE-X and GEICAM trials tested these approaches .
An Abbreviated History Of Adjuvant Systemic Therapy
The initial approach to therapy for breast cancer was based on the premise that the disease metastasized via locoregional spread in an orderly fashion, and thus could be cured with aggressive surgery. The radical mastectomy was thus the standard surgical procedure for breast cancer in the early 20th century . Randomized trials subsequently showed no benefit from radical mastectomy compared with less aggressive surgical procedures, and demonstrated that distant recurrence remained a major clinical problem irrespective of the primary surgical therapy .
Table 1 Systemic adjuvant therapy options for operable breast cancer
Side Effects Of Chemotherapy
Chemotherapy damages cells as they divide. This makes the drugs effective against cancer cells, which divide rapidly. However, some normal cells such as hair follicles, blood cells and cells inside the mouth or bowel also divide rapidly. Side effects happen when chemotherapy damages these normal cells. Unlike cancer cells, normal cells can recover, so most side effects are temporary.
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Choosing A Chemo Combination
Your doctor will probably talk to you about combining different chemo drugs. They may refer to them by abbreviations for their names. Some of the most common include:
- AC: Adriamycin and Cytoxan
- CMF: Cytoxan, methotrexate, and fluorouracil
- FAC: Fluorouracil, Adriamycin, and Cytoxan
- CAF: Cytoxan, Adriamycin, and fluorouracil
Common Chemotherapy Drugs For Breast Cancer
Chemotherapy drugs used to treat early breast cancer include:
- Taxanes: This class of drugs includes docetaxel and paclitaxel .
These drugs are often used with others like carboplatin, cyclophosphamide , and fluorouracil .
These drugs are often used with others like carboplatin , cyclophosphamide , and fluorouracil .
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What Are The Potential Side Effects Of Chemotherapy Drugs
The specific side effects you may experience will depend on the type and amount of medications you are given and how long you are taking them. The most common temporary side effects include:
- Higher risk of infection
- Bruising or bleeding
- Premature menopause and infertility are potential permanent complications of chemotherapy.
- Heart damage can be a permanent complication of some chemotherapy.
Please contact your health care provider about specific side effects you can expect to experience from your specific chemotherapy medications. Also discuss troubling or unmanageable side effects with your provider.
Who Needs Breast Cancer Chemotherapy
Chemotherapy is offered to most patients based on several factors including:
- Type of receptors and status
- Number of lymph nodes involved and degree of involvement
- The risk for cancer to spread elsewhere in the body
Your medical team will work to select the right blend of chemotherapy drugs to suppress each stage of the cancer cells growth.
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Adjuvant And Neoadjuvant Drugs
- Ixabepilone
- Eribulin
Although drug combinations are often used to treat early breast cancer, advanced breast cancer more often is treated with single chemo drugs. Still, some combinations, such as paclitaxel plus gemcitabine, are commonly used to treat advanced breast cancer.
For cancers that are HER2-positive, one or more drugs that target HER2 may be used with chemo.
Third Generation Chemotherapy Regimens
Docetaxel, doxorubicin, and cyclophosphamide
Unlike paclitaxel, docetaxel does not have a major pharmacokinetic interaction with doxorubicin, and does not increase doxorubicin-related cardiotoxicity when given concurrently . Two studies compared a combination of docetaxel, doxorubicin, and cyclophosphamide with FAC . The Breast Cancer International Research Group 0001 trial compared six cycles DAC with FAC every 3 weeks as adjuvant treatment for 1,491 women with operable node-positive breast cancer . After a median follow-up of 124 months, there were improvements in DFS and OS . The benefit in DFS was irrespective of nodal, hormone receptor, and HER2 status. The GEICAM 9805 trial compared six cycles of DAC with FAC in 1,060 patients with node-negative breast cancer . After a median follow-up of 77 months, there was a significant improvement in DFS and a trend toward improved OS favoring DAC. In both trials, DAC was associated with considerably more toxicity, including febrile neutropenia.
Sequential FEC-taxane therapy
Dose dense sequential doxorubicin/cyclophosphamide-paclitaxel
Sequential AC-weekly paclitaxel or every 3 week docetaxel
Sequential versus concurrent taxane administration
Predicting benefit from chemotherapy
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Will I Be Able To Work While I Am Having Treatment
Most women are able to continue working during chemotherapy if they wish to. If you plan to keep working, it helps to have a supportive work place that gives you flexible work hours. You may need to have a few days off after each cycle of chemotherapy and when you get back to work you may find it difficult to work long hours. Your doctor can provide a medical certificate for time off this can be just a few days or a few months depending on your individual situation.
Chemo Only Contributes About 2% To Overall 5
This is probably also something that your doctors didnt mention.
It is important to remember that the 2.1% average can be deceptive. Some cancers do respond better to chemo than others.
According to this research, the best results from chemotherapy are in treating testicular cancer.
In testicular cancer, chemo is 41.8% effective toward 5-year survival.
In Hodgkins Disease, chemo is 35.8% effective toward 5-year survival.
Still not great. Would you hire an auto mechanic who had a 42% success rate at fixing cars?
You can read and download the entire study HERE.
Make sure you look at the tables on page 3 and 4. These tables show the survival rate in the US and Australia, with chemo treatments, for each type of cancer.
You will notice that the survival rate for some cancers after chemo treatment has a dash . That means ZERO effectiveness of chemotherapy toward 5-year survival. This includes pancreatic cancer, soft tissue sarcoma, melanoma, kidney, bladder, and uterine cancers.
And yet chemotherapy is still prescribed to treat many these cancers today, over a decade after this study was published.
And although not included in this research, chemo does have a better success rate on leukemia and some childhood cancers.
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Why Is Chemotherapy Still The Go
So why in the world are doctors continuing to prescribe a treatment that doesnt work on most cancers?
Read my post on The Business of Chemo.
When I was where you are, back in 2004, I also knew chemo was a toxic poison, which is why I didnt want to do it.
It didnt make sense to me that I could poison my body back to health.
Nevertheless, in the back of my mind it was my last resort if nothing else worked.
Today, as Im writing this post, I know many people , whose bodies have been wrecked by chemotherapy.
Theyve spent tens of thousands of dollars on these treatments and they still have cancer.
That is why I do what I do here on this site.
I am not a doctor and cannot give cancer treatment advice, but as a friend I can certainly share what I did.
Theres no law against that!
Purpose Of Neoadjuvant Chemotherapy
All systemic therapy given for non-metastatic, invasive breast cancer is intended to reduce the risk of your cancer returning. But the purpose of administering it prior to surgery is to shrink your tumor or stop the spread of cancer to make surgery less invasive and more effective.
This process, called downstaging, may make it possible for you to have less extensive surgery on the breast and/or axilla , especially for those with large tumors. By having the size of the tumor reduced, you may become a candidate for surgical resection or breast-conserving surgery rather than mastectomy.
Neoadjuvant chemotherapy has also been shown to improve cosmetic outcomes and reduce postoperative complications such as lymphedema, particularly in those who undergo breast reconstruction surgery.
Up to half of the patients undergoing neoadjuvant treatment may become suitable candidates for breast conservation rather than mastectomy.
One systematic review of neoadjuvant chemotherapy for operable breast cancer found that those who received chemotherapy before surgery had a lower mastectomy rate than those undergoing some surgical procedure before being given chemotherapy.
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How Do You Get Chemotherapy For Breast Cancer
You get chemotherapy as a pill or in a vein daily, weekly, or every 2-4 weeks. You may get one drug or a combination of them. Your treatment plan is designed for your particular situation.
If your veins are hard to find, you may get a catheter in a large vein. These devices are inserted by a surgeon or radiologist and have an opening to the skin or a port under the skin, allowing chemotherapy medications to be given. They can also be used to give fluids or take blood samples. Once chemotherapy is finished, your catheter will be removed.
How Will I Know If The Chemotherapy Treatments Are Working
Some people may think that their chemotherapy treatment is not working if they do not experience side effects. However, this is a myth.
If you are receiving adjuvant chemotherapy , it is not possible for your doctor to directly determine whether the treatment is working because there are no tumor cells left to assess. However, adjuvant chemotherapy treatments have been proven helpful in studies in which some women were given chemotherapy, while others were not. If you are receiving chemotherapy for metastatic disease, the effects will be monitored, routinely, by blood tests, scans, and/or other imaging studies. These may include CT scans, bone scans, and/or X-rays).
After completing adjuvant chemotherapy, your doctor will evaluate your progress through periodic physical examinations, routine mammography, and appropriate testing if a new problem develops.
Last reviewed by a Cleveland Clinic medical professional on 09/05/2013.
References
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What Are The Side Effects Of Oral Chemotherapy
The possible side effects of oral chemotherapy are the same as those of traditional chemotherapy, and may include fatigue, nausea, diarrhea, constipation or hair loss.
The potential side effects you may experience depend on the type of chemotherapy drug youre taking and how often youre taking it. Not everyone experiences the same ones or in the same way. Patients are sometimes surprised to find out that not all chemotherapies cause hair loss, for example, or that men and women may experience different side effects of chemotherapy.
We also have more ways to help patients tolerate treatment these days. Anti-nausea medications have improved significantly over the years and are frequently given along with chemotherapy drugs. Supportive care therapies are designed to help prevent and manage side effects of cancer and its treatment. At CTCA®, for example, our patients have access to our integrative care services, including:
Your oncologist may be able to change the dosage of your medication or even prescribe a different chemotherapy if necessary. Talk to your care team about your options if you experience side effects.
Is Oral Chemotherapy As Effective As Iv Chemotherapy
Yes, the potential results are the same no matter which method you choose. The purpose of chemotherapy is to kill cancer cells. It has the potential to reduce the size of tumors, control disease progression and, in some cases, may lead to cancer regression.
Chemotherapy may be used before and/or after another treatment, such as surgery, or alone as the primary treatment method. Its sometimes used in combination with other treatments, such as radiation therapy or immunotherapy.
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Changes In Bowel Habit
Chemotherapy drugs and the anti-nausea drugs used with them may cause diarrhoea or constipation. Constipation is an annoyance but can usually be easily managed with laxatives. Diarrhoea is sometimes an important warning sign that develops with particular chemotherapy drugs. If you get diarrhoea you should let your oncologist or nurse know. You will be given specific advice about how to manage it.
How Effective Is Chemotherapy For Breast Cancer Treatment
Chemotherapy treatment utilizes special drugs that are administered either orally or intravenously to destroy cancerous cells. These drugs generally travel to all parts of the body through the bloodstream. Normally, chemotherapy is used for treating early-stage invasive breast cancers. It is designed to eliminate any remaining cancerous cells following surgery & for reducing risk of recurrence of breast cancer. Chemotherapy is also utilized for destroying advanced-stage breast cancer or for the purpose of damaging cancerous cells. Moreover, in some patients, chemotherapy is also given prior to operation in order to shrink the size of cancerous tumors before surgical intervention.
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Chemotherapy Drugs Used For Breast Cancer
Chemotherapy is found to be most effective when combinations of chemo drugs are used. However, doctors nowadays use several different combinations & no single combination is yet recognized as the best. Common chemotherapy drugs used for treating breast cancer include the following. Most often combinations involving 2 or 3 of these drugs are normally used.
- Carboplatin
Toxicity And Dose Modifications
Toxicity was evaluated according to National Cancer Institute of CancerClinical Trials Group criteria by clinical and laboratory evaluations at day 21 of each cycle. If creatinine/blood urea nitrogen was up to 1.5, the upper normal value cisplatin was omitted. In case of constipation, mucositis, or diarrhea , the next cycle of chemotherapy was postponed by 1 or 2 weeks until recovery and then administered at 75% of the dose. The treatment was postponed by 1 week if the blood count on day 21 showed a neutrophil count < 1,000/mm3 and/or platelet count < 100,000 mm3. If on day 28 the neutrophil count was > 1,000/mm3 and platelet count > 100,000 mm3, the treatment was readministered. Otherwise, treatment was postponed by another week. If after 2 weeks of treatment delay hematologic recovery was not obtained, treatment was discontinued.
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Can I Still Work While Receiving Chemotherapy Treatments For Breast Cancer
Yes. Most people are able to continue working while they are being treated with chemotherapy. You may have to adjust your work schedule while receiving chemotherapy, especially if you have side effects. It may be possible to schedule your treatments later in the day or right before the weekend so they don’t interfere as much with your work schedule.
What Are The Side Effects
Chemotherapy is sometimes referred to as a systemic treatment, because it affects all parts of your body. Unfortunately, it can attack fast-growing healthy cells, such as hair follicles, as well as cancer cells. This causes unwanted side effects such as fatigue, nausea and hair loss. Your medical oncologist or oncology nurse can give you information on ways to manage these side effects.
If side effects are affecting your daily life, its important to discuss them with a member of your medical team. In some instances, your oncologist may be able to change your chemotherapy drug to one that has fewer side effects.
Chemotherapy drugs all work differently and have different side effects. Not all women will suffer side effects from chemotherapy. If you dont experience side effects, it does not mean that the drugs aren’t working.
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Adherence: Carefully Following Instructions
Taking a pill to treat your cancer may sound easier than it is. Non-adherence, or not taking the drug correctly and on time, may have serious consequences, including the inability to treat your cancer and/or harm caused to yourself or others. Patients who choose to self-administer their chemotherapy must be committed to doing so correctly, and need to be organized enough to follow through on that commitment.
Chemotherapy drugs may be toxic and must be stored and handled very carefully. They must be kept away from children. You may have to wear gloves when handling them. You must be able to follow all safety precautions.
You also need to take oral chemotherapy drugs according to precise instructions. Some need to be taken at a certain time every day, with or without food. Others may need to be taken on a rotating schedule, similar to that of an infusion schedule, depending on your treatment regimen. Its even more challenging if, like many patients, youre juggling multiple medications, especially if the schedule differs daily and/or weekly.
The ability to do this is crucial, however. Not taking chemotherapy drugs correctly could increase their toxicity, which is very dangerous, or it could decrease the absorption, which means youre not getting the right amount to treat your cancer. Missed doses mean the drugs cant adequately fight cancer.
Even with the best of intentions, it may be difficult to properly adhere to an oral treatment regimen.
What To Expect After Chemo
Once youâre home, you need to take care of yourself and take steps to manage chemo side effects. These include:
- Take medications the doctor prescribed for side effects.
- Stay away from anyone with a cold or infection — chemo makes it harder for your body to fight germs.
- Drink lots of fluids for the first 8 hours to move the medicine through your body.
- Manage bodily fluids and waste that may have traces of chemo. Usually, this means flushing the toilet twice.
Youâll see your doctor every 4 to 6 months for the next 5 years after treatment ends.
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