Cycle length: 21 days.
Total cycles: 4 (for advanced disease). |
| Drug | Dose and route | Administration | Given on days |
| Cisplatin | 20 mg/m2 IV per day | Dilute with 250 mL normal saline (NS) and administer over one hour. Do not administer with aluminum needles or intravenous sets. | Days 1 through 5 |
| Etoposide | 100 mg/m2 IV per day | Dilute with 500 mL NS (concentration less than 0.4 mg/mL) and administer over one hour. | Days 1 through 5 |
| Pretreatment considerations: |
| Hydration | - Induction of diuresis using at least 2000 mL of intravenous NS minimizes the risk of cisplatin nephrotoxicity. Fluid administration should be adequate to establish a urine flow of at least 100 mL/hour 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.
|
| Vesicant/irritant properties | - Both cisplatin and etoposide are irritants. Cisplatin can cause significant tissue damage; avoid extravasation.[2]
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
|
| Infection prophylaxis | - The decision to administer primary prophylaxis with G-CSF is individualized, since the rate of febrile neutropenia with this regimen ranges from 10 to 20%.[3,4] UpToDate contributors offer prophylactic G-CSF support to patients age ≥50 years due to the increased risk of febrile neutropenia in this population.[5]
- 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 | - A lower initial dose of etoposide may be needed for patients with kidney or hepatic dysfunction.[6]
- Dose adjustment of cisplatin in the setting of baseline kidney impairment requires a balanced discussion of the goals of treatment and the risks of cisplatin nephrotoxicity.
- 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.
|
| Monitoring parameters: |
- CBC with differential weekly during treatment.
|
- Basic metabolic panel (creatinine and electrolytes) prior to each treatment cycle.
|
- Liver function tests prior to each treatment cycle.
|
- Monitor for neurotoxicity; monitor for hearing loss prior to each dose of cisplatin; audiometry as clinical indicated.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - In general, dose reductions and dose delays for myelotoxicity should be minimized or avoided since treatment intent is curative.[2,7]
- For patients who remain neutropenic at the start of a cycle, several approaches are available:
- Proceed with chemotherapy regardless of the hematologic parameters on day 1. If the granulocyte count remains ≤2500 cells/microL or platelets ≤100,000 cells/microL on day 5, then omit day 5 etoposide.[1]
- or
- Proceed with chemotherapy if the absolute neutrophil count is ≥500 cells/microL and platelets are ≥90,000/microL. If values do not meet these parameters, delay treatment for up to 1 week.[8]
- For patients who experience febrile neutropenia, prophylactic G-CSF should be administered for additional cycles. For patients who experience febrile neutropenia despite G-CSF prophylaxis, UpToDate contributors administer antibiotic prophylaxis for future cycles.
- Dose reductions of chemotherapy for febrile neutropenia are not advised. Such dose reductions can lead to inferior cancer-specific outcomes,[9] which are more likely to occur than severe sepsis from subsequent cycles without dose reduction.
- 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.
|
| Neurologic toxicity | - Neuropathy usually is seen after cumulative doses of cisplatin beyond 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.
|
| Kidney toxicity | - Treatment in the setting of kidney impairment (ie, creatinine >2.0 mg/dL or GFR <50 mL/min) requires a balanced discussion of the goals of treatment and the risks of cisplatin nephrotoxicity in the face of impaired kidney function.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
