Cycle length: 21 days.
Total cycles: 4 cycles. |
| Drug | Dose and route | Administration | Given on days |
| Docetaxel | 75 mg/m2 IV | Dilute in 250 mL NS or D5W* to a final concentration of 0.3 to 0.74 mg/mL, and administer over 60 minutes. | Day 1 |
| Cyclophosphamide | 600 mg/m2 IV | Dilute in 250 to 500 mL NS or D5W* and administer over 30 to 60 minutes after docetaxel. | Day 1 |
| Pretreatment considerations: |
| Hydration | - Patients receiving cyclophosphamide should maintain adequate oral hydration (2 to 3 L/day during treatment and one to two days thereafter) and void frequently to reduce the risk of hemorrhagic cystitis.[2]
- Refer to UpToDate topics on hemorrhagic cystitis in cancer patients.
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| Emesis risk | - MODERATE (between 30 and 90% frequency of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Prophylaxis for infusion reactions | - Premedication with dexamethasone 8 mg twice daily for three days, starting one day prior to docetaxel administration, is recommended.[3] Glucocorticoid pretreatment also reduces the incidence of docetaxel-induced fluid retention. If a severe infusion reaction to docetaxel occurs (chest tightness, wheezing, hypoxia, loss of consciousness), docetaxel should be immediately discontinued. However, if the reaction is minor (eg, flushing or localized skin reaction), the infusion can be continued or it can be temporarily interrupted, and restarted at 50% of the initial rate once symptoms have resolved. The rate can then be increased if tolerated. Management of infusion reactions and issues related to rechallenge are discussed separately.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
|
| Vesicant/irritant properties | - Docetaxel and cyclophosphamide are both classified as irritants.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
|
| Infection prophylaxis | - All cycles should be administered with myeloid growth factor support.
- 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 dysfunction | - Docetaxel should not be administered to patients with a serum bilirubin above the ULN or to patients with transaminase elevations >1.5 times ULN in conjunction with alkaline phosphatase >2.5 times 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.
|
| Dose adjustment for baseline kidney dysfunction | - Dose adjustment is not necessary for docetaxel in kidney impairment. The need for cyclophosphamide dose reduction in kidney insufficiency is controversial.
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with kidney impairment, conventional cytotoxic agents.
|
| 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.[3] 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 on day 1 prior to each cycle.
|
- Serum electrolytes and liver and kidney function tests every two weeks prior to each treatment cycle.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Docetaxel 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).[3]
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| Hepatotoxicity | - Docetaxel dose reduction may be needed for patients who develop significant alterations in transaminases and ALP during therapy.
- 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.
|
| 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, the dose of docetaxel should be reduced from 75 to 60 mg/m2.[3] If toxicity persists, treatment should be discontinued.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
