Cycle length: 14 days.
Total cycles: 4. |
| 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.* The presence of local erythematous streaking along the vein as well as facial flushing may be signs that administration is too rapid. 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. Rapid infusions may produce nasal burning or congestion that is relieved by slowing the rate. | Day 1 |
| After complete of AC, administer: |
| Paclitaxel | 175 mg/m2 IV | Dilute with 250 to 500 mL NS or D5W* (final concentration of 0.3 to 1.2 mg/mL) and administer over three hours.¶ | 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.
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| Prophylaxis for infusion reactions | - Paclitaxel may cause severe hypersensitivity reactions. Premedication regimen should include dexamethasone (either 20 mg orally 12 and 6 hours before, or 20 mg IV 30 minutes before drug administration) plus both an H1 (diphenhydramine 25 to 50 mg IV) and an H2 receptor antagonist (famotidine 20 mg IV) 30 to 60 minutes prior to paclitaxel administration. Severe infusion reactions (eg, skin rash, flushing, dyspnea, urticaria, back pain, hypotension, chest pain, tachycardia) occur primarily during the first and second infusions, typically within the first hour after the start of the infusion. Further information on infusion reactions, including management, is available.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
|
| 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. Paclitaxel can cause significant tissue damage; avoid extravasation.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
|
| Infection prophylaxis | - Hematopoietic growth factors (filgrastim [G-CSF] 5 mcg/kg subcutaneously rounded to 300 mcg or 480 mcg on days 3 through 10, or pegfilgrastim 6 milligrams subcutaneously on day 2 or 3) with each cycle is required with each cycle of dose-dense AC. It is also suggested during the dose-dense paclitaxel part of the regimen, although a prospective, single-arm study found that omission of pegfilgrastim was feasible, with only 10% of patients needing a paclitaxel dose delay or reduction due to neutropenia.[4]
- 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 baseline liver or kidney dysfunction | - Dose adjustment is not necessary for doxorubicin or paclitaxel in kidney impairment. The need for cyclophosphamide dose reduction in kidney insufficiency is controversial. For patients with preexisting hepatic impairment, dose adjustments in doxorubicin, cyclophosphamide, and paclitaxel may be needed.
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with kidney impairment, 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.
|
| Cardiac issues | - 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] A baseline assessment of LVEF is recommended, with periodic reassessment of during therapy. 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.
|
- Assess changes in neurologic function prior to each treatment cycle of paclitaxel.
|
- During treatment with doxorubicin or paclitaxel, assess line site periodically during infusion of chemotherapy for signs and symptoms of extravasation.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Subsequent cycles should be delayed until the ANC is >1000/microL and platelet count >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.
|
| Neurologic toxicity | - For patients who develop severe neuropathy (grade 3 or 4) that persists for a week or longer, the dose of paclitaxel should be reduced by 20% for subsequent courses of paclitaxel; hold if severe toxicity persists after dose reduction.[5]
- Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
|
| Dose adjustment for liver or kidney dysfunction | - Guidelines for managing doxorubicin, cyclophosphamide, and paclitaxel 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 impairment, 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.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
