| Cycle length: 28 days. |
| Drug | Dose and route | Administration | Given on days |
| Cisplatin | 75 mg/m2 IV | Dilute in 250 mL NS* and administer over 60 minutes. Do not administer with aluminum needles or sets. Alternative: Dilute in 2000 mL D5W* in 1/2 or 1/3 NS* containing 37.5 g of mannitol and infuse over six to eight hours.[2] Do not administer with aluminum needles or sets. | Day 1 |
| Fluorouracil (FU) | 750 mg/m2 per day IV | Dilute in 500 to 1000 mL D5W* and administer as a continuous infusion over 24 hours per day for five days (120 hours). Begin after completion of cisplatin on day 1. To accommodate an ambulatory pump for outpatient treatment, can be administered undiluted (50 mg/mL) or the total dose can be diluted in 100 to 150 mL NS.* | Days 1 through 5 |
| Pretreatment considerations: |
| Hydration | - IV fluid to establish a urine flow of at least 100 mL/hour for at least two hours prior to and two hours after cisplatin administration.
- Alternative: Pretreatment hydration with 1 to 2 L of fluid infused for 8 to 12 hours prior to each dose of cisplatin.[2]
- Supplemental electrolytes as per institutional guidelines.
- Refer to UpToDate topics on cisplatin nephrotoxicity.
|
| 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 | - Routine prophylaxis is not indicated.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
|
| Vesicant/irritant properties | - Cisplatin and FU are irritants but can cause significant tissue damage with a large volume, concentrated extravasation; avoid extravasation.[2,3]
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
|
| Infection prophylaxis | - Routine primary prophylaxis with granulocyte colony stimulating factors not warranted.
- 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 | - The optimal approach to cisplatin therapy in patients with preexisting renal impairment is unknown.[2] A lower starting dose of FU may be needed for patients with liver impairment.[3]
- 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: |
- CBC with differential prior to each new treatment cycle.
|
- Assess electrolytes and liver and renal function prior to each new treatment cycle.
|
- Monitor for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.
|
- Assess change in neurologic function prior to each treatment.
|
- Monitor for diarrhea, stomatitis, and cutaneous toxicity (palmar-plantar erythrodysesthesias).
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Hold new cycle of treatment until neutrophil count ≥1500/microL and platelet count >100,000/microL. Reduce dose of cisplatin and FU by 20% for nadir grade 4 thrombocytopenia persisting longer than five days or febrile neutropenia requiring hospitalization and antibiotics.
|
| Diarrhea | - Hold both cisplatin and FU for grade 4 diarrhea until complete resolution and then resume with a 20% dose reduction for both drugs.
- NOTE: Severe diarrhea and mucositis after FU should prompt evaluation for dihydropyrimidine dehydrogenase deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
|
| Nephrotoxicity | - Hold cisplatin until serum creatinine is <1.5 mg/dL and/or blood urea nitrogen is <25 mg/dL. For grade 2 or greater nephrotoxicity during treatment (creatinine >1.5 times normal value despite adequate hydration), creatinine clearance should be determined prior to next cycle, and cisplatin dose reduced if <60 mL/min.[2]
- Alternatively, consider substitution of carboplatin for cisplatin if renal impairment (creatinine clearance <50 mL/min).
|
| Neurologic toxicity | - Neuropathy usually is seen with cumulative doses of cisplatin >400 mg/m2, although there is marked interindividual variation. Patients with mild neuropathy can continue to receive full cisplatin doses. However, if the neuropathy interferes with function, the risk of potentially disabling neurotoxicity must be weighed against the benefit of continued treatment.
- Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
- 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.[3]
|
| Palmar-plantar erythrodysesthesia | - For grade 4 palmar-plantar erythrodysesthesia, withhold treatment until complete resolution then resume with a 20% dose reduction of both cisplatin and FU.
- Refer to UpToDate topics on cutaneous complications of conventional chemotherapy agents.
|
| Stomatitis | - For grade 4 mucositis, hold next cycle until complete resolution and resume with 20% dose modification. For grade 3 mucositis, reduce cisplatin and FU doses by 20%.
- Refer to UpToDate topics on oral toxicity associated with chemotherapy.
|
| Cardiotoxicity | - Cardiotoxicity observed with FU includes myocardial infarction/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, electrocardiographic changes, and cardiomyopathy. There is no recommended dose for resumption of FU administration following development of cardiac toxicity, and the drug should be discontinued.[3]
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
