Cycle length: 28 days.
Total cycles: 6. |
| Drug | Dose and route | Administration | Given on days |
| Cyclophosphamide | 600 mg/m2 IV | Dilute with 250 mL NS or D5W* and administer over 30 to 60 minutes. | Days 1 and 8 |
| Methotrexate | 40 mg/m2 IV | Drug is available in a 25 mg/mL solution that needs no further dilution. It can be administered as a slow IV push. | Days 1 and 8 |
| Fluorouracil (FU) | 600 mg/m2 IV | Drug is available in a 50 mg/mL solution that needs no further dilution prior to administration as IV push. | Days 1 and 8 |
| Pretreatment considerations: |
| Hydration | - Patients receiving cyclophosphamide should maintain adequate oral hydration (2 to 3 L/day) and void frequently to reduce risk of hemorrhagic cystitis.[2]
- Refer to UpToDate topics on hemorrhagic cystitis in cancer patients.
|
| Emesis risk | - MODERATE (30 to 90% frequency of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Prophylaxis for infusion reactions | - No specific premedication regimen is indicated.
|
| Infection prophylaxis | - Primary prophylaxis with G-CSF is not indicated.[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 baseline liver or renal dysfunction | - Lower starting dose of methotrexate may be needed in patients with renal impairment and in those with third space fluid collections (eg, ascites, pleural effusion).[3] Methotrexate should not be administered in the setting of severe liver impairment (total bilirubin >4 × ULN).[4] A lower starting dose of FU may be needed for patients with liver impairment. A lower starting dose of cyclophosphamide may be needed in patients with renal impairment.
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with renal 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.
|
| Monitoring parameters: |
- Assess CBC with differential on days 1 and 8 of each treatment cycle.
|
- Assess serum electrolytes and liver and renal function tests on or prior to day 1.
|
- Monitor for diarrhea and cutaneous toxicity (palmar-plantar erythrodysesthesias).
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - If the ANC ≤1500/microL or platelets ≤100,000/microL on day 1 and day 8 of each cycle, therapy should be delayed until counts recover.
|
| Dose adjustment for diarrhea | - Withhold FU for grade 2 or worse diarrhea and restart at a lower dose after complete resolution.
- NOTE: Severe diarrhea and mucositis after FU should prompt evaluation for DPD deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
|
| Palmar-plantar erythrodysesthesia | - Hold FU for grade 2 or greater palmar-plantar erythrodysesthesia, and reduce subsequent dose by 20%.[1]
- Refer to UpToDate topics on cutaneous complications of conventional chemotherapy agents.
|
| Neurologic toxicity | - There is no recommended dose for resumption of FU administration following development of hyperammonemic encephalopathy, acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances; the drug should be permanently discontinued.[5]
|
| Cardiotoxicity | - Cardiotoxicity observed with FU includes myocardial infarction/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, ECG changes, and cardiomyopathy. There is no recommended dose for resumption of FU administration following development of cardiac toxicity, and the drug should be discontinued.[5]
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
