| Cycle length: 21 days. |
| Drug | Dose and route | Administration | Given on days |
| Docetaxel | 75 mg/m2 IV | Dilute in 250 mL NS* to a final concentration of 0.3 to 0.74 mg/mL and administer over 60 minutes. | Day 1 |
| Cisplatin | 75 mg/m2 IV | Dilute in 250 mL NS* and administer over 60 minutes. Do not administer with aluminum needles or IV 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. For use in an ambulatory infusion pump. 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 two hours before and two hours after cisplatin administration.
- Refer to UpToDate topics on cisplatin nephrotoxicity.
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| Emesis risk | - HIGH (>90% frequency of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - Premedicate with dexamethasone prior to docetaxel administration.[1]
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
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| Vesicant/irritant properties | - Docetaxel and cisplatin are irritants, but can cause significant tissue damage; avoid extravasation.[2,3]
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
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| Infection prophylaxis | - Primary prophylaxis with G-CSF indicated (incidence of neutropenic fever 29%[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.
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| Dose adjustment for baseline liver or kidney dysfunction | - Docetaxel should not be given if serum bilirubin is above the ULN, or if the AST and/or ALT >1.5 times the ULN concomitant with AP >2.5 times the ULN.[3] Dose modifications of FU may be needed for patients with hepatic impairment.[4] The optimal approach to cisplatin therapy in patients with preexisting kidney impairment is unknown; such patients were excluded from the original trial.[1]
- Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents; chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents; and 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: |
- Assess CBC with differential and platelet count prior to each cycle of treatment.
|
- Assess basic metabolic panel including creatinine and electrolytes, and liver function tests prior to each treatment cycle.
|
- Monitor for neurotoxicity, diarrhea, and palmar-plantar erythrodysesthesias prior to each treatment cycle.
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- Monitor for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.
|
- Patients with kidney impairment, hyperuricemia, and bulky tumors are at risk for TLS and should undergo correction of dehydration and lowering of high serum uric acid levels prior to treatment initiation, and be closely monitored for TLS during and after treatment.
- Refer to UpToDate topics on tumor lysis syndrome.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Patients should not be retreated until neutrophils recover to >1500/microL and platelets recover to >100,000/microL.[3] If the platelet count declines to <25,000/microL during therapy, reduce subsequent doses of docetaxel by 20%. After the first episode of ANC <1000/microL lasting >7 days or febrile neutropenia or neutropenic infection despite G-CSF support, reduce docetaxel dose by 20%.[3,5] For a second episode, reduce subsequent doses of docetaxel by another 20%.
|
| Kidney dysfunction | - Hold cisplatin until serum creatinine <1.5 mg/dL and/or BUN <25 mg/dL.[2] For grade ≥2 nephrotoxicity during treatment (creatinine >1.5 times normal value despite adequate rehydration), creatinine clearance should be determined prior to next cycle and cisplatin dose reduced if <60 mL/min.
|
| Neurotoxicity | - Neuropathy usually is seen with cumulative doses of cisplatin >400 mg/m2, although there is marked interindividual variation. Reduce cisplatin dose 20% for grade ≥2 peripheral neuropathy and discontinue for grade 3 neuropathy.[2,5]
- 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.[6]
|
| Gastrointestinal toxicity | - Hold FU treatment for grade 3 or worse diarrhea and restart at a lower dose after complete resolution. For the first episode of grade 3 diarrhea or grade 3 or 4 stomatitis, reduce FU by 20%; subsequent episodes, reduce docetaxel 20%.[3] First episode of grade 4 diarrhea, reduce both docetaxel and FU by 20%; subsequent episodes, discontinue treatment.
- NOTE: Severe diarrhea, mucositis, and myelosuppression 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%.[6]
- Refer to UpToDate topics on cutaneous complications of conventional chemotherapy agents.
|
| Hepatotoxicity | - Docetaxel should not be given if serum bilirubin is above the ULN, or if the AST and/or ALT >1.5 times the ULN concomitant with AP >2.5 times the ULN.[3] For intracycle increases of AST/ALT >2.5 but ≤5 times the ULN, and AP <2.5 times the ULN or AST/ALT >1.5 to ≤5 times the ULN and AP >2.5 to ≤5 times the ULN, reduce docetaxel by 20%.[3] Discontinue docetaxel if AST/ALT >5 times the ULN and/or AP >5 times the ULN.
|
| 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.[6]
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
