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Treatment Name: Dose Dense AC (DD-AC, Doxorubicin + Cyclophospha­mide)

Dose Dense AC (DD-AC, Doxorubicin + Cyclophospha­mide) is a Chemotherapy Regimen for Breast Cancer - early stage

How does Dose-Dense AC work?
Each of the medications in AC (Adriamycin and Cytoxan) are designed to kill cancer cells or slow growth of cancer cells.

A - Adriamycin® (doxorubicin)
C - Cyclophosphamide (Cytoxan®)

Goals of therapy:
Dose-Dense AC can be given either before surgery (neoadjuvant) to shrink the size of the tumor, or after surgery (adjuvant) to remove any remaining cancer cells that may be still present in the body. Dose-Dense AC is usually given with the goal of cure.

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Schedule

  • Doxorubicin intravenous (I.V.) push or infusion over 5 to 15 minutes on Day 1
  • Cyclophosphamide I.V. infusion over 30 to 60 minutes on Day 1

Estimated total infusion time for adriamycin and cytoxan:

  • Up to two hours (this includes pre-medications)
  • Infusion times are based on clinical studies, but may vary depending on doctor preference or patient tolerability.  Pre-medications and intravenous (I.V.) fluids, such as hydration, may add more time

Dose-Dense AC is usually given in an outpatient infusion center, allowing the person to go home afterwards.

Dose-Dense AC is repeated every 14 days. This is known as one Cycle. Each cycle may be repeated up to four times, depending upon the stage of the disease. Duration of therapy may last up to two to three months, depending upon response, tolerability, and number of cycles prescribed.

Click here for common dose dense AC (DDAC) starting doses

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Side Effects

In a multi-drug regimen, each medication has unique side effects. When these medicines are given together, drug-related side effects reported in clinical studies give the best estimate of what to expect. In clinical studies, the most commonly reported side effects with Dose-Dense AC are shown here:

Note: although the rate of neutropenic fever was not reported in the original clinical studies using dose dense AC, it can be common (more than 20%) without the use of medicines designed to prevent neutropenic fever

Side effect videos Side Effect Videos
Neutropenic FeverNeutropenic FeverPainPainNausea and VomitingNausea and VomitingFatigue Fatigue DiarrheaDiarrheaAnemiaAnemiaHair LossHair Loss

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Monitoring

How often is monitoring needed?
Labs (blood tests) may be checked before each chemotherapy cycle. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), plus any others your doctor may order.

How often is imaging needed?
Imaging is checked before treatment and may be also checked after several cycles. Imaging may include: magnetic resonance imaging (MRI), computerized tomography (CT) scans, or positron emission tomography (PET) scans.

How might blood test results/imaging affect treatment?
Depending upon the results, your doctor may advise to continue Dose-Dense AC as planned, or delay or switch therapy.

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ChemoExperts Tips

  • Drink plenty of fluids (1 - 2 liters per day), especially on days when cyclophosphamide is given. This will help flush the bladder and avoid bladder toxicity from a break-down product (metabolite) of cyclophosphamide called acrolein. Adequate fluid intake may also help prevent nausea or vomiting
  • Typically, filgrastim (Neupogen®) or pegfilgrastim (Neulasta®) is given after dose dense AC chemotherapy to stimulate production of white blood cells and avoid periods of neutropenia
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
  • Clinical trials may exist for breast cancer. Ask your doctor if any studies are currently enrolling in your area. If not, go to clinicaltrials.gov to search for other centers offering study medications

Patient Assistance & Co-payment Coverage

Patients under the age of 65 years, or those with private insurance plans:
If you have insurance and are looking for patient assistance or copay assistance for Dose Dense AC (DD-AC, Doxorubicin + Cyclophospha­mide), we have provided links that may help.

Visit our Patient Assistance page and click the links to various patient assistance programs for help paying for Dose Dense AC (DD-AC, Doxorubicin + Cyclophospha­mide). Depending upon your income, they may be able to help cover the cost of:

  • Adriamycin®
  • Cyclo­phospha­mide IV

For Branded medications (may be available for generic medications too), check with the manufacturer to determine if a co-pay card is offered and if it could reduce your monthly copay.

  • If you are uninsured, check with the manufacturer to determine if you are eligible to receive medication at no cost.

Medicare and Medicaid patients (Patients 65 years or older):
The clinic providing treatment will likely pre-authorize medications and immune therapies such as Dose Dense AC (DD-AC, Doxorubicin + Cyclophospha­mide) and are the best source to help you understand drug cost.

  • Ask to speak with a patient assistance technician or financial counselor at the clinic or hospital administering this therapy.

Emotional Wellness

What is Emotional Wellness?
Emotional wellness is having a positive outlook balanced with a realistic understanding of current life events. This requires both an awareness and acceptance of your emotions. It is with this knowledge that you can develop a plan to take the necessary actions to positively impact your life.

Emotional wellness uses an ongoing process to continually reflect on the stressors of life in a constructive manner to move forward and create happiness.

Because emotional wellness is deeply connected with physical, social, and spiritual wellness, pursuing it often becomes particularly difficult in times of major illness. Despite this difficulty, working toward emotional wellness has been connected to improved treatment outcomes and a higher likelihood of achieving goals of therapy.

Learn more about pursuing emotional wellness while receiving treatment with Dose Dense AC (DD-AC, Doxorubicin + Cyclophospha­mide)

Individual Drug Label Information

Adriamycin® (Doxorubicin)

  • Doxorubicin is administered as an intravenous infusion and is red in color
  • Can affect heart function. A heart study (echocardiogram) may be required before receiving the first dose
  • Dosage may be reduced in patients with poor liver function
  • Has been linked to the development of other cancers in a small number of people (1.5% chance at 10 years)
General Doxorubicin (Adriamycin) Side Effects
  • Nausea, vomiting, diarrhea, and mouth sores (stomatitis)
  • Leakage into skin or surrounding muscle during infusion may cause severe irritation (extravasation)
  • May temporarily turn urine orange
  • Hair loss, which is usually reversible
  • Increased risk of infection due to decrease white blood cell count (neutropenia)
  • Click on the doxorubicin (Adriamycin) package insert below for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaHair LossHair LossFatigue Fatigue PainPainAnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Cyclo­phospha­mide IV (Cytoxan®)

  • Cyclophosphamide is administered as an intravenous (I.V.) infusion
  • May decrease the ability to become pregnant. Fertility preservation is recommended in couples wishing to become pregnant.
  • A smaller dosage may be required for patients receiving hemodialysis
  • Has been linked to the development of other cancers in a small number of people
General Cyclophosphamide (Cytoxan) Side Effects
  • Low white blood cell count which can increase the risk of infection
  • Nausea or vomiting, which can be acute (first 24 hours) or delayed (Days 2 – 5)
  • Hair loss, which is usually reversible
  • Click on the cyclophosphamide (Cytoxan) package insert below for reported side effects and potential drug Interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingHair LossHair LossNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

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References

Citron ML, Berry DA, Cirrincione C, et al. Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21:1431-1439.

Created: October 13, 2015 Updated: May 1, 2018

What is Breast Cancer - early stage?

What is Early Stage Breast Cancer?
A disease of either the milk-producing glands known as lobules, or milk ducts, or other cells found in the breast. Early stage breast cancer may also affect the lymph nodes, but has not usually spread to other areas of the body. Breast cancer is the most common type of cancer diagnosed in women, but may rarely affect men as well. Breast cancer cells may have increased expression of estrogen receptors (ER positive or negative), progestin receptors (PR positive or negative), and/or HER-2 receptors (HER-2 positive or negative). The presence or lack of these receptors will help determine the most effective chemotherapy medications to give.

Genetic causes, such as the BRCA (pronounced "Bracka") mutation, significantly increase the risk of developing breast cancer. Other risk factors for breast cancer include family history of breast cancer, high fat diet, and obesity. The stage of breast cancer can vary at diagnosis and throughout treatment. Stages of breast cancer include I, II, III, and IV. The effectiveness of the treatment may depend upon the stage at diagnosis.

Types of breast cancer:
1. Hormone-receptor positive or negative (60 - 65% of patients)

  • Estrogen Receptor positive (ER)+ or negative (ER)-
  • Progestin Receptor positive (PR)+ or negative (PR)-

2. Hormone Epidermal growth factor Receptor-2 (HER-2) positive or negative (20 - 25% of patients)

  • HER-2 + (positive)
  • HER-2 -  (negative)

3. Triple Negative (15 - 18% of patients)

  • ER- and PR- and (HER-2)-
NOTE: Treatment Options listed below are not all-inclusive. Other treatments may be available. ChemoExperts provides drug information and does not recommend any one treatment over another. Only your Doctor can choose which therapy is appropriate for you.

Common Starting Doses

  • Doxorubicin 60 mg/m2 intravenous (I.V.) push or infusion over 5 to 15 minutes on Day 1
  • Cyclophosphamide 600 mg/m2 I.V. infusion over 30 to 60 minutes on Day 1

Cycle is 14 days.

What is a CBC?

A Complete Blood Count (CBC) is a frequently ordered blood test that tells clinicians the status of your: 1) White blood cell count, 2) Hemoglobin, and 3) Platelet count at the time the test was taken.

Common uses:
1) White blood cell count (WBC): is used to determine infection risk, or response to chemotherapy. Certain chemotherapy agents may harm our good infection-fighting cells. Sometimes chemotherapy may need to be delayed to allow these cells to recover.

2) Hemoglobin: is used to determine if someone is anemic. Anytime the hemoglobin is below 12 g/dL, the person is said to be anemic. Red blood cell transfusions, and sometimes iron can be given to restore the hemoglobin level, but anemia treatment should always aim at treating the underlying cause or condition.

3) Platelet count: is used to determine if the risk of bleeding is increased or if a platelet transfusion is required to prevent bleeding. Certain medications that increase bleeding risk, such as: aspirin, certain chemotherapy agents, and blood thinners, may need to be stopped temporarily until the platelet count is within a safe range.

What is a CMP?

A Comprehensive Metabolic Panel (CMP) is a frequently ordered blood test that tells clinicians the status of your: 1) Electrolytes & Acid/Base status2) Kidney function, 3) Liver function, 4) Blood sugar, and 5) Calcium at the time the test was taken. It is commonly used to monitor liver and kidney function when beginning new medications such as chemotherapy. A total of 14 tests are run simultaneously and are shown below.

Electrolytes & Acid/Base status:
1) Sodium, 2) Potassium, 3) Carbon dioxide, 4) Chloride

Kidney Function:
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)

Liver Function:
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein

Blood sugar:
13) Serum glucose

Calcium:
14) Serum calcium

What does "Cure" mean?

The word “cure” means there are no cancer cells left in the body and cancer will never come back. Depending on the cancer type and stage, this may be the true goal of therapy. However, it is very difficult to prove all cancer cells are gone. Even though images, like X-rays and MRI’s, and blood tests may not show any signs of cancer, there can be a small amount of cancer cells still left in the body. Because of this, doctors use the word “remission” is used more often. This means there are no signs or symptoms of cancer. Patients in remission are followed closely for any signs of cancer returning. Sometimes, more chemotherapy may be given while in remission to prevent the cancer from coming back.

Doctors usually do not consider a patient “cured” until the chance of cancer returning is extremely low. If cancer does return, it usually happens within 5 years of having a remission. Because of this, doctors do not consider a patient cured unless the cancer has not come back within 5 years of remission. The five-year cutoff does not apply to all cancers.

What is acrolein?

It is a breakdown product (metabolite) of cyclophosphamide. If too much acrolein builds up in the bladder, it harms the cells lining the bladder and causes bleeding. Hydration, by mouth or I.V. infusion, helps lessen the risk of this side effect.

What is Neutropenia?

This occurs when there is an abnormally low amount of a certain type of white blood cells, called neutrophils, in the blood. These neutrophils help the body fight infections caused by bacteria and viruses. Many chemotherapy drugs temporarily damage bone marrow where white blood cells are created, resulting in neutropenia. Please watch our video on neutropenic fever to learn more.