| Cycle length: 21 days. Duration of therapy: 6 cycles. |
| Drug | Dose and route | Administration | Given on days |
| Doxorubicin | 50 mg/m2 IV | Dilute with NS* to a final concentration of 2 mg/mL and administer 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.[1,2] | Day 1 |
| Cyclophosphamide | 500 mg/m2 IV | Dilute with 250 to 500 mL NS or D5W* and administer over 30 to 60 minutes. Alternatively, cyclophosphamide can be diluted after reconstitution with NS or D5W* and given as slow IV infusion over five minutes (for doses up to 2 grams).[1,3] | Day 1 |
| Docetaxel | 75 mg/m2 IV | Given one hour after cyclophosphamide. Dilute in 250 mL NS* to a final concentration of 0.3 to 0.74 mg/mL and administer over 60 minutes.[1,4] | 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.
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| Emesis risk | - HIGH (>90% frequency of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Prophylaxis for infusion reactions | - Dexamethasone premedication (8 mg orally every 12 hours for six doses beginning the day before treatment started) should be given to prevent docetaxel-related hypersensitivity and fluid retention.[1,4]
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| Vesicant/irritant properties | - Doxorubicin is a vesicant and can cause significant tissue damage if 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.
- Docetaxel is an irritant but can cause significant tissue damage; avoid extravasation.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
|
| Infection prophylaxis | - Primary prophylaxis with antimicrobials was implemented in this study. Patients received ciprofloxacin 500 mg twice daily on days 5 through 14 of each cycle. Primary prophylaxis with G-CSF was not permitted. However, secondary prophylaxis with G-CSF (administered on days 4 through 11) was mandatory after an episode of febrile neutropenia or infection in subsequent cycles.[1]
|
| Dose adjustment for baseline liver or renal dysfunction | - Dose adjustment is not necessary for doxorubicin and docetaxel in renal impairment. A lower starting dose of cyclophosphamide may be needed in patients with baseline renal dysfunction.
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency, conventional cytotoxic agents.
- A lower starting dose for cyclophosphamide and doxorubicin may be needed in patients with hepatic impairment. Docetaxel should not be administered to patients with a serum bilirubin above the ULN or to patients with transaminase elevations >1.5 times the ULN.
- 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 | - Doxrubicin is associated with cardiomyopathy, the incidence of which is related to cumulative dose. Assess baseline LVEF prior to administration. Doxorubicin is contraindicated for patients with recent myocardial infarction, severe myocardial dysfunction, severe arrhythmia, or previous therapy with high cumulative doses of doxorubicin or any other anthracyclines.[2]
- Refer to UpToDate topics on clinical features, diagnosis, and staging of newly diagnosed breast cancer; clinical manifestations, monitoring, and diagnosis of anthracycline-induced cardiotoxicity; and prevention and management of anthracycline cardiotoxicity.
|
| Dose adjustment for known drug interactions | - Caution is required if administering docetaxel with strong CYP3A4 inhibitors.¶ According to the United States Prescribing Information, avoid the use of docetaxel with strong CYP3A4 inhibitors (if possible). If concomitant therapy cannot be avoided, monitor closely for toxicity and consider a docetaxel dose reduction.[4] Docetaxel dose reductions for concomitant therapies should be individualized based on patient factors (eg, performance status) and the intent of therapy (ie, curative or palliative).
- Refer to "Suggested dose modifications for toxicity" below.
|
| Monitoring parameters: |
- CBC with differential and platelet count every three weeks prior to each treatment cycle.
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- Serum electrolytes and liver and renal function tests every three weeks prior to each treatment cycle.
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- Cumulative doxorubicin dose should be monitored. Reassess LVEF periodically during TAC therapy as clinically indicated.
|
- Patients with renal impairment, hyperuricemia, and bulky tumors are at risk for TLS and should undergo correction of dehydration and lowering of high serum uric acid levels prior to treatment initiation, and be closely monitored for TLS during and after treatment.
- Refer to UpToDate topics on tumor lysis syndrome.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - A new cycle of chemotherapy should only be administered if the ANC is >1500/microL. A 25% dose reduction of docetaxel is recommended for subsequent cycles in patients who develop severe prolonged neutropenia (<500/microL lasting seven days or more), febrile neutropenia, or a grade 4 infection (ie, an infection with life-threatening consequences).[4]
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| Hepatotoxicity | - Docetaxel dose reduction may be needed for patients who develop significant alterations in transaminases and alkaline phosphatase during therapy.[4]
- 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.
|
| 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.
- Discontinue treatment for any clinically significant cardiac event.
|
| Cutaneous, mucosal, and neurologic toxicity | - For severe or cumulative cutaneous reactions (erythema and desquamation), grade 3 or 4 stomatitis, or moderate neurosensory signs and/or symptoms, reduce docetaxel dose.[4] Discontinue if toxicity persists.
- Discontinue treatment for any grade 4 toxicity and any grade 3 toxicity that recurs despite dose reduction.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
