Cycle length: 21 days.
Total cycles: 4 cycles (in the adjuvant setting). |
| Drug | Dose and route | Administration | Given on days |
| Doxorubicin | 60 mg/m2 IV | Dilute with NS* to a final concentration of 2 mg/mL and administered as an IV bolus over three to five minutes into a free-flowing IV infusion of NS or D5W.* If needed, doxorubicin can be further diluted after reconstitution in NS or D5W* and given as a slow IV infusion administered over 15 to 60 minutes.[2] | Day 1 |
| Cyclophosphamide | 600 mg/m2 IV | Dilute with 250 to 500 mL NS or D5W* and administer over 30 to 60 minutes. | Day 1 |
| Pretreatment considerations: |
| Hydration | - Patients receiving cyclophosphamide should maintain adequate oral hydration (2 to 3 L/day during administration and for one to two days thereafter) and void frequently to reduce the risk of hemorrhagic cystitis.[3]
- Refer to UpToDate topics on hemorrhagic cystitis in cancer patients.
|
| Emesis risk | - HIGH (>90% frequency of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Vesicant/irritant properties | - Doxorubicin is a vesicant and can cause significant tissue damage if an extravasation occurs. For peripheral infusions, the IV line should be recently placed into a large, intact vein, with good blood return established immediately prior to starting the infusion. The IV or catheter site should be continuously monitored throughout drug administration infusion. If extravasation occurs, apply ice to the site and consider use of dexrazoxane.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
|
| Infection prophylaxis | |
| Dose adjustment for baseline liver or kidney dysfunction | - Dose adjustment is not necessary for doxorubicin in kidney impairment. The need for cyclophosphamide dose reduction in kidney insufficiency is controversial. For patients with preexisting hepatic impairment, dose adjustments in doxorubicin and cyclophosphamide may be needed.
- Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents and chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents.
|
| Cardiac issues | - A baseline assessment of LVEF is recommended, with periodic reassessment of during therapy. The risk of doxorubicin-associated cardiac dysfunction is related to cumulative dose. The risk is increased in patients with underlying heart disease, when anthracyclines are used concurrently with other cardiotoxic agents or radiation, and in patients previously treated with mediastinal or chest wall irradiation. Doxorubicin is contraindicated for patients with recent myocardial infarction, severe myocardial dysfunction, severe arrhythmia, or previous therapy with high cumulative doses of doxorubicin.[2] Further information on anthracycline-associated cardiotoxicity, including discussion about prevention and treatment, is available.
- Refer to UpToDate topics on clinical manifestations, monitoring, and diagnosis of anthracycline-induced cardiotoxicity and prevention and management of anthracycline cardiotoxicity.
|
| Monitoring parameters: |
- CBC with differential and platelet count every two weeks prior to each treatment cycle.
|
- Serum electrolytes and liver and kidney function tests every two weeks prior to each treatment cycle.
|
- Cumulative doxorubicin dose should be monitored. As appropriate, assess cardiac function prior to initiation of AC then periodically during treatment. For patients receiving AC for metastatic disease, consider the addition of dexrazoxane after 300 mg/m2 total dose.
- Refer to UpToDate topics on clinical manifestations, monitoring, and diagnosis of anthracycline-induced cardiotoxicity and prevention and management of anthracycline cardiotoxicity.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Subsequent cycles should be delayed until the ANC is greater than 1000/microL and platelet count greater than 100,000/microL. If there is more than a three-week delay in treatment, a dose reduction of 25% is recommended.[1]
- Refer to UpToDate topics on use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
|
| Dose adjustment for hepatic or kidney dysfunction | - Guidelines for managing doxorubicin and cyclophosphamide in patients who have changes in kidney or liver function during therapy are addressed in detail separately.
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with kidney insufficiency, conventional cytotoxic agents; chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents; and chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents.
|
| Cardiotoxicity | - Guidelines for managing doxorubicin in patients with symptomatic cardiac dysfunction or asymptomatic changes in LVEF during therapy are addressed in detail separately.
- Refer to UpToDate topics on clinical manifestations, monitoring, and diagnosis of anthracycline-induced cardiotoxicity and prevention and management of anthracycline cardiotoxicity.
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
