| Cycle length: 21 days. |
| Drug | Dose and route | Administration | Given on days |
| Paclitaxel | 135 mg/m2 IV | Dilute in 500 mL normal saline (NS) or 5% dextrose in water (D5W) and administer over 24 hours.* | Day 1 |
| Cisplatin | 50 mg/m2 IV | Dilute with 250 mL 0.09% sodium chloride for injection and administer at a rate of 1 mg/min immediately after paclitaxel. Do not administer with aluminum needles or intravenous sets. | Day 1 |
| Pretreatment considerations: |
| Hydration | - Induction of diuresis using intravenous NS minimizes the risk of cisplatin nephrotoxicity. Fluid administration should be adequate to establish a urine flow of at least 100 mL/hour for two hours prior to 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 plus both an H1 and an H2 receptor antagonist prior to paclitaxel administration.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
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| Vesicant/irritant properties | - Paclitaxel 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.
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| Infection prophylaxis | - Primary prophylaxis with G-CSF not indicated.
- 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 | - Dose reductions are required for cisplatin in kidney insufficiency. The optimal approach to cisplatin therapy in patients with preexisting kidney impairment is unknown. Patients with a serum creatinine level >2 mg/dL were excluded from the original trial.[1] For patients with preexisting hepatic impairment, dose adjustments for paclitaxel may be needed.[2]
- 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.
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| Monitoring parameters: |
- CBC with differential and platelet count weekly during treatment.
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- Basic metabolic panel (creatinine and electrolytes) prior to each treatment cycle.
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- Liver function tests prior to each treatment cycle.
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- Monitor neurotoxicity and monitor for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Repeat cycles should not begin until the ANC count is >1500 cells/microL and platelets are >100,000/microL. Reduce paclitaxel to 110 mg/m2 for grade 3 or 4 neutropenic fever or grade 4 thrombocytopenia. If patients have an episode of febrile neutropenia or persistent neutropenia that prevents treatment on schedule, secondary prevention with support-CSF is suggested in addition to a reduction in paclitaxel dose to 110 mg/m2.
- 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.
|
| Neurotoxicity | - Reduce cisplatin dose to 25 mg/m2 and paclitaxel dose to 90 mg/m2 for grade 2 neurotoxicity or ototoxicity and discontinue treatment for ≥grade 3 neurotoxicity.[1] 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 conventional non-platinum cancer chemotherapy.
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| Nephrotoxicity | - Withhold treatment for persistent elevation of creatinine to >2 mg/dL.[1] If elevation persists more than six weeks after a previous dose, discontinue cisplatin.
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| Nausea and vomiting | - Reduce cisplatin dose to 37.5 mg/m2 for grade 4 nausea and vomiting uncontrolled with appropriate anti-emesis support (refer to "Emesis risk" above).
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| Hepatotoxicity | - Repeat cycles should not begin until the bilirubin ≤1.5 times normal, and aspartate aminotransferase and alkaline phosphatase are ≤3 times normal.[1] Discontinue paclitaxel for grade 3 or 4 hepatotoxicity.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
