Cycle length: 28 days.
Total cycles: 6. |
| Drug | Dose and route | Administration | Given on days |
| Cyclophosphamide* | 100 mg/m2 orally daily | Cyclophosphamide tablets should be swallowed whole, and not cut or crushed before administration. | Days 1 through 14 |
| Methotrexate | 40 mg/m2 IV | Methotrexate 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 per day IV | FU is available in 50 mg/mL solution that needs no further dilution prior to administration as IV push. | Days 1 and 8 |
| Pretreatment considerations: |
| Hydration | - Patients taking cyclophosphamide should maintain adequate hydration (2 to 3 L/day), void frequently, and avoid taking cyclophosphamide at bedtime to reduce the risk of bladder irritation.
- 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 prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults.
|
| Dose adjustment for baseline liver or kidney dysfunction | - 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 kidney impairment. A lower starting dose of methotrexate may be needed in patients with kidney impairment and in those with third-space fluid collections (eg, ascites, pleural effusion).[2] Methotrexate should not be administered in the setting of severe liver impairment (total bilirubin >4 x ULN).[3]
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with kidney insufficiency, conventional cytotoxic agents and chemotherapy hepatotoxicity and dose modication in patients with liver disease.
|
| Monitoring parameters: |
- CBC with differential and platelet count on days 1 and 8 of each treatment cycle.
|
- Serum electrolytes, kidney, and liver function once per cycle on day 1.
|
- Monitor for diarrhea and cutaneous toxicity.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - If the ANC is <1000/microL or platelets are <75,000/microL on day 1 of each cycle, therapy should be delayed until counts recover, at which time 75% of the calculated dose should be administered, or 100% of the dose if the ANC is >2000/microL and the platelet count is ≥100,000/microL. If the ANC on day 8 is <1000/microL or platelets <75,000/microL, the day 8 doses of methotrexate and FU should be omitted.[1]
|
| Dose adjustment for diarrhea | - Withhold FU for grade 2 or worse diarrhea and restart at a lower dose after complete resolution.
- NOTE: Severe diarrhea, mucositis, and myelosuppression after FU should prompt evaluation for DPD deficiency.
- Refer to UpToDate topics on enterotoxicty of chemotherapeutic agents.
|
| Palmar-plantar erythrodysesthesia | - Hold FU for grade 2 or greater palmar-plantar erythrodysesthesia, and reduce subsequent dose by 20%.[4]
- 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.[4]
|
| 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.[4]
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
