| Cycle length: Every 21 days for four cycles. |
| Drug | Dose and route | Administration | Given on days |
| Cisplatin | 60 mg/m2 IV | Dilute in 250 mL normal saline (NS) and administer over 60 minutes. Do not administer with aluminum needles or sets. | Day 1 |
| Etoposide | 120 mg/m2 IV daily | Dilute in 500 mL NS* or 5% dextrose in water (D5W) to final concentration <0.4 mg/mL. Infuse over 30 to 60 minutes; if infused more rapidly, severe hypotension may occur. | Days 1, 2, and 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 | - HIGH.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Prophylaxis for infusion reactions | - Routine prophylaxis not indicated.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
|
| Vesicant/irritant properties | - Cisplatin is an irritant 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 hematopoietic growth factors is not recommended.
- 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 preexisting kidney impairment is unknown. Such patients were excluded from the original trial.[1] A lower starting dose of etoposide may be needed for patients with kidney or liver impairment.[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.
|
| Monitoring parameters: |
- CBC with differential and platelet count weekly during treatment.
|
- Basic metabolic panel (creatinine and electrolytes) and liver function tests prior to each cycle.
|
- Monitor for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Day 1 ANC should be >1500 cells/microL and platelets should be >75,000/microL for treatment during each cycle. Etoposide dose reductions should be based on the following table, taking into account the nadir ANC and platelet count along with day 1 ANC and platelet count for each cycle.[1]
|
| Etoposide dose | Nadir ANC (cells/mm) | Nadir platelet count per microL | Day 1 ANC | Day 1 platelet |
| 25% reduction | 750 to 999 | 50,000 to 99,999 | >2000 | >100,000 |
| 50% reduction | <750 | <50,000 | >2000 | |
| Hold | <750 | <50,000 | 1500 to 2000 | 75,000 to 100,000 |
| Neurotoxicity | - Neuropathy usually is seen with cumulative doses of cisplatin >400 mg/m2, although there is marked interindividual variation.
- Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
|
| 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.
- Refer to UpToDate topics on cisplatin nephrotoxicity.
|
| Other severe non-hematologic toxicity | - Etoposide and cisplatin should be withheld or doses decreased depending on clinical judgement.
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
