| Cycle length: Every 28 days, for four cycles. |
| Drug | Dose and route | Administration | Given on days |
| Vinorelbine | 25 mg/m2 IV | Dilute in normal saline (NS) to a final concentration between 0.5 and 2 mg/mL and administer over 6 to 10 minutes into the side port of a free-flowing IV infusion. | Days 1, 8, 15, and 22 |
| Cisplatin | 50 mg/m2 IV | Dilute in 250 mL NS and administer over two hours. Do not administer with aluminum needles or sets. | Days 1 and 8 |
| 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.
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| Emesis risk | - HIGH: Days 1 and 8;
MINIMAL: Days 15 and 22. - Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Vesicant/irritant properties | - Vinorelbine is a vesicant and 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 hematopoietic growth factors is not recommended (incidence of febrile neutropenia is 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.
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| Dose adjustment for baseline liver or kidney dysfunction | - A lower starting dose of vinorelbine may be needed for patients with hepatic impairment. 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.
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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 for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Treatment with vinorelbine should be delayed until ANC is greater than 1500 cells/microL based on the manufacturer's guidelines. A dose reduction of 50% is recommended for patients with ANC 1000/microL to 1500/microL. If a patient's ANC is <1000/microL, the weekly dose of vinorelbine should be held and blood counts should be rechecked in one week. For patients who develop febrile neutropenia or who have had two consecutive weekly doses held, the following dose adjustments will apply for subsequent doses of vinorelbine. For ANC ≥1500/microL, use a 25% dose reduction. For ANC 1000/microL to 1400/microL, use a 62.5% dose reduction. If ANC remains <1000/microL, hold vinorelbine doses until count recovery and then follow above dosing guidelines.[2]
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| Neurotoxicity | - 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.
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| Nephrotoxicity | - Hold cisplatin until serum creatinine <1.5 mg/dL and/or blood urea nitrogen <25 mg/dL. For grade ≥2 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.
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| Hepatotoxicity | - The United States Prescribing Information recommends dose reduction for patients who develop hyperbilirubinemia during treatment with vinorelbine:
- Serum bilirubin ≤2.0 mg/dL, give 100% of dose
- Serum bilirubin 2.1 to 3.0 mg/dL, give 50% of dose
- Serum bilirubin >3.0 mg/dL, give 20% of dose
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
