| Cycle length: Chemotherapy for 12.5 weeks and radiotherapy for five weeks. |
| Drug | Dose and route | Administration | Given on days¶ |
| Cisplatin | 75 mg/m2 IV | Dilute in 250 mL NS* and administer over 30 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 a six to eight hour period.[2] Do not administer with aluminum needles or sets. | Days 1 and 29 |
| Fluorouracil (FU) | 1000 mg/m2 per day IV | Dilute in 500 to 1000 mL D5W* and administer as continuous infusion over 24 hours for four days (96 hours). Administer after completion of cisplatin. | Days 1 through 4, and days 29 through 32 |
| Radiotherapy (45 to 59 Gy) | 1.8 Gy per day, five days per week | Begin within 24 hours of the administration of chemotherapy. | Start on day 1 (total of five weeks) |
| 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) with high potential for delayed emesis on days 1 to 4, 29 to 32, 57 to 60, and 85 to 88.
LOW risk on other days. - Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults and radiotherapy-induced nausea and vomiting.
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| 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 | - Primary prophylaxis with G-CSF not indicated; use of G-CSF should be avoided in patients receiving concomitant chemoradiotherapy.[4]
- 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. A lower starting dose of FU may be needed for patients with liver impairment.
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency, conventional cytotoxic agents and chemotherapy hepatoxicity and dose modification in patients with liver disease.
|
| Monitoring parameters: |
- CBC with differential prior to each new chemotherapy cycle.
|
- Assess electrolytes and liver and renal function prior to each new chemotherapy 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:Δ |
| Myelotoxicity | - Doses of cisplatin and FU were reduced by 50% for grade 4 neutropenia or febrile neutropenia during therapy.[1] Temporarily suspend chemoradiotherapy for grade 3 or 4 neutropenia until recovery to grade ≤2.
|
| Diarrhea | - The original protocol did not specify a dose reduction scheme for diarrhea. Others suggest holding all therapy for grade 3 or worse gastrointestinal toxicity during combined modality treatment, and reinitiation after resolution to grade 1 with a dose reduction of FU.[5]
- NOTE: Severe diarrhea, mucositis, and myelosuppression after FU should prompt evaluation for DPD deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
|
| Nephrotoxicity | - Hold cisplatin until serum creatinine is <1.5 mg/dL and/or BUN is <25 mg/dL.[2] 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.
|
| 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. In one study, cisplatin dose was reduced for "moderate" neurotoxicity.[5]
- 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]
|
| Stomatitis | - Reduce dose of FU for grade 3 stomatitis or esophagopharyngitis.[5]
- 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, 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.[3]
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
