| Cycle length: 14 days. |
| Drug | Dose and route | Administration | Given on days |
| Docetaxel | 40 mg/m2 IV | Dilute with 250 mL NS* to a final concentration of 0.3 to 0.74 mg/mL and administer over 60 minutes. | Day 1 |
| Leucovorin¶ | 400 mg/m2 IV | Dilute with 250 mL D5W* and administer over two hours. | Day 1 |
| Fluorouracil (FU) | 400 mg/m2 IV bolus | Slow IV push over five minutes. Administer immediately after leucovorin. | Day 1 |
| FU | 2000 mg/m2 IV | Dilute with 500 to 1000 mL D5W* and administer by continuous infusion for 48 hours starting immediately after the FU bolus 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.* | Day 1 |
| Cisplatin | 40 mg/m2 IV | Dilute with 250 mL NS* and administer over 60 minutes. Do not administer with aluminum needles or IV sets. | Day 3 |
| 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.
- Refer to UpToDate topics on cisplatin nephrotoxicity.
|
| Emesis risk | - Day 1 and 2: LOW;
Day 3: HIGH. - Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Prophylaxis for infusion reactions | - Premedicate with dexamethasone prior to docetaxel administration.
- 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.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
|
| Infection prophylaxis | - Primary prophylaxis with G-CSF not justified (incidence of neutropenic fever approximately 7%[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 kidney dysfunction | - The optimal approach to cisplatin therapy in patients with pre-existing kidney impairment is unknown. Patients with serum creatinine >1.5 mg/dL were excluded from the original trial.[1] Docetaxel should not be given to patients with a serum bilirubin above the ULN or to those with transaminase elevations >1.5 times ULN in conjunction with AP >2.5 times ULN.[2] Lower starting doses of FU may be needed for severe hepatic impairment.
- 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 insufficiency, conventional cytotoxic agents.
|
| Dose adjustment for known drug interactions | - Caution is required if administering docetaxel with strong CYP3A4 inhibitors.Δ 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.[2] 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 on day 1 prior to each new course of treatment.
|
- Assess basic metabolic panel including creatinine and electrolytes, and liver function tests prior to each new treatment course.
|
- Monitor for neurotoxicity, diarrhea, and fluid retention prior to each treatment cycle.
|
- 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 with subsequent cycles of modified DCF until neutrophils recover to ≥1000/microL and platelets recover to >75,000/microL. Reduce docetaxel dose by 10 mg/m2 for febrile neutropenia, grade 3 or 4 neutropenia for ≥7 days, or platelet count ≤75,000/microL on the day of treatment.[1]
|
| Nephrotoxicity | - Withhold cisplatin until serum creatinine is ≤2 mg/dL.[1,3] Reduce cisplatin dose by 10 mg/m2 for serum creatinine of 1.8 or 1.9 mg/dL.
|
| Neurotoxicity | - Neuropathy usually is seen with cumulative doses of cisplatin >400 mg/m2, although there is marked interindividual variation. Docetaxel can also cause both sensory and motor neuropathy, the incidence of which is related to cumulative dose. Patients with mild neuropathy can continue to receive full cisplatin and docetaxel doses. However, if the neuropathy interferes with function, the risk of potentially disabling neurotoxicity must be weighed against the benefit of continued treatment. The protocol recommended a 10 mg/m2 reduction in cisplatin dose for grade 3 or 4 ototoxicity and a 10 mg/m2 reduction in docetaxel dose for grade ≥2 peripheral neuropathy.[1]
- 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]
|
| Gastrointestinal toxicity | - After resolution of toxicity, reduce FU and leucovorin doses for grade 3 or 4 diarrhea or stomatitis.[4] The protocol suggested initial dose reduction from 400 to 300 mg/m2 for the bolus dose of both FU and leucovorin, and a reduction from 1000 to 800 mg/m2 per day for the infusional FU.[1] Reduce cisplatin dose by 10 mg/m2 for grade 4 nausea or vomiting or grade 3 nausea or vomiting for >5 days.
- NOTE: Severe diarrhea, mucositis, and myelosuppression after FU should prompt evaluation for DPD deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
|
| Hepatotoxicity | - Hold docetaxel for bilirubin 1.5 to 2.0 mg/dL or total bilirubin one to two times ULN, or for AST/ALT >5 times ULN, or AP >5 times ULN, or AST/ALT >2 but ≤5 times the ULN and AP >3 times ULN, or AST/ALT >1 to ≤2 times ULN and AP >5 times ULN.[1] Reduce docetaxel dose by 10 mg/m2 if AST/ALT >2 but ≤5 times ULN and AP >1 but ≤3 times ULN or AST/ALT >1 but ≤2 times ULN and AP >3 but ≤5 times ULN.[1]
|
| 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.[4]
|
| Other toxicity | - Hold chemotherapy for any other grade 3 to 4 nonhematologic toxicity (with exception of grade 3 electrolyte abnormalities or grade 3 anemia not associated with bleeding).
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
