From the Guidelines
Cisplatin and etoposide should be administered at doses of 20 mg/m² and 100 mg/m², respectively, on days 1-5, repeated every 21 days, as part of the EP regimen. This regimen is commonly used for the treatment of testicular cancer and other malignancies, as supported by the guidelines outlined in the study by 1. The EP regimen consists of cisplatin 20 mg/m² and etoposide 100 mg/m², both administered intravenously on days 1-5, with cycles repeated every 21 days.
Administration and Monitoring
Cisplatin requires pre-hydration with 1-2 liters of IV fluids, along with anti-emetics and corticosteroids to prevent severe nausea and vomiting. Etoposide should be administered as a slow infusion over 30-60 minutes to reduce the risk of hypotension. Regular monitoring of complete blood counts, renal function, electrolytes, and audiometry is essential throughout treatment. Dose adjustments may be necessary based on toxicities, particularly for renal impairment with cisplatin and myelosuppression with both agents.
Mechanism of Action
This regimen works by different mechanisms - cisplatin forms DNA crosslinks while etoposide inhibits topoisomerase II - providing synergistic antitumor activity against rapidly dividing cancer cells. The study by 1 also supports the use of cisplatin and etoposide in combination for the treatment of malignant germ cell tumors. Additionally, the study by 1 outlines the EP regimen as a primary chemotherapy regimen for germ cell tumors, further supporting its use in clinical practice.
Clinical Considerations
In clinical practice, the choice of chemotherapy regimen depends on various factors, including the type and stage of cancer, patient performance status, and potential contraindications to certain agents. The EP regimen is a well-established and effective treatment option for patients with testicular cancer and other malignancies, and its use is supported by the guidelines outlined in the studies by 1, 1, and 1.
From the FDA Drug Label
DOSAGE AND ADMINISTRATION Cisplatin is administered by slow intravenous infusion. CISPLATIN SHOULD NOT BE GIVEN BY RAPID INTRAVENOUS INJECTION. The usual cisplatin dose for the treatment of testicular cancer in combination with other approved chemotherapeutic agents is 20 mg/m 2IV daily for 5 days per cycle. The drug is then diluted in 2 liters of 5% Dextrose in 1/2 or 1/3 normal saline containing 37. 5 g of mannitol, and infused over a 6 hour to 8 hour period.
Administration of Cisplatin and Etoposide:
- Cisplatin should be administered by slow intravenous infusion over a 6 hour to 8 hour period.
- The dose of cisplatin for testicular cancer is 20 mg/m 2IV daily for 5 days per cycle.
- However, the label does not provide information on the administration of etoposide.
- Since the label does not provide direct information on the administration of cisplatin and etoposide together, no conclusion can be drawn about the administration of this specific combination 2.
From the Research
Administration of Cisplatin and Etoposide
- Cisplatin administration requires hydration to prevent nephrotoxicity, and the administration of magnesium and mannitol may assist in maintaining renal function and reducing nephrotoxicity in adults 3.
- Etoposide can be administered orally or intravenously, with no statistical differences observed in progression-free survival (PFS) or overall survival (OS) when comparing patients receiving long infusion, short infusion, or oral etoposide 4.
- Hydration is important for patients receiving carboplatin, especially those with impaired renal function or receiving high doses of the drug 5.
Nephrotoxicity Considerations
- Nephrotoxicity is a prominent component of the toxicity profile of platinum-based chemotherapy, including cisplatin and carboplatin 5.
- Acute nephrotoxicity occurred in 29% of patients treated with high-dose carboplatin, etoposide, and ifosfamide, and was associated with higher transfusion requirements, more overall toxicities, and a longer hospital stay 6.
- Research has uncovered many of the cellular mechanisms underlying cisplatin-induced renal cell death, including inflammation provoked by injury to renal epithelial cells 7.
Hydration Management
- Hydration in conjunction with appropriate diuresis can decrease the incidence of nephrotoxicity in patients receiving cisplatin therapy 3.
- Mannitol may be useful in selected settings for patients receiving cisplatin, while furosemide is probably not generally useful 5.
- Detailed suggestions regarding the protection of kidney function when using platinum-based compounds are presented in the literature 5.