Etoposide and Cisplatin Dosing for NSGCT
For patients with non-seminomatous germ cell tumors (NSGCT), administer etoposide 100 mg/m² IV on days 1-5 and cisplatin 20 mg/m² IV on days 1-5, repeated every 21 days, with the number of cycles determined by IGCCCG risk stratification: 4 cycles for good-risk disease or 3 cycles of BEP (if bleomycin is tolerated) for good-risk, and 4 cycles of BEP for intermediate/poor-risk disease. 1
Risk-Stratified Treatment Approach
Good-Risk NSGCT (Stage IIC and IIIA)
- Four cycles of EP is the standard regimen when bleomycin is contraindicated or not preferred 1
- Alternatively, three cycles of BEP (bleomycin, etoposide, cisplatin) can be used if bleomycin is tolerated 1
- Both regimens cure approximately 90% of good-risk patients 1
- The EP regimen achieves a 98% favorable response rate and 98% disease-specific survival 2, 3
Intermediate-Risk NSGCT (Stage IIIB)
- Four cycles of BEP is the standard regimen 1
- If bleomycin is contraindicated, use four cycles of VIP (etoposide 75 mg/m² days 1-5, ifosfamide 1200 mg/m² days 1-5, cisplatin 20 mg/m² days 1-5), though this is more myelotoxic 1
- Cure rate is approximately 70% with standard therapy 1
Poor-Risk NSGCT (Stage IIIC)
- Four cycles of BEP remains the standard regimen 1
- Monitor tumor marker decline after the first cycle: patients with unfavorable marker decline should be switched to dose-dense chemotherapy regimens 1
- Fewer than half achieve durable complete response with standard BEP, making clinical trial enrollment preferred when available 1
Critical Dosing and Schedule Details
Standard EP Regimen Specifications
- Etoposide: 100 mg/m² IV daily on days 1-5 1
- Cisplatin: 20 mg/m² IV daily on days 1-5 1
- Cycle interval: Repeat every 21 days without delay or dose reduction 1
- Full-dose administration is critical for optimal outcomes 2, 3
When to Choose EP Over BEP
EP should be strongly preferred in patients with:
- Age >40 years (increased bleomycin pulmonary toxicity risk) 1
- Active smoking or vaping/e-cigarette use 2
- Pre-existing pulmonary disease 1
- Reduced or borderline kidney function 2
- Cumulative bleomycin dose concerns (>300 units) 4
Stage-Specific Considerations
Stage IIA NSGCT with Normal Markers
- Nerve-sparing RPLND is the recommended initial treatment when performed by experienced surgeons at specialized centers 1
- For stage IIA with elevated markers, treat as metastatic good- or intermediate-risk disease with 3-4 cycles of BEP 1
Stage IIA/B NSGCT with Elevated Markers
- Treat as metastatic disease according to IGCCCG risk group 1
- Use three cycles of BEP for good-risk or four cycles of BEP for intermediate-risk 1
Common Pitfalls and How to Avoid Them
Dosing Errors
- Never reduce doses or delay cycles unless medically necessary—this compromises cure rates 1
- In the recent Memorial Sloan Kettering cohort, 96.3% of patients received full-dose EPx4, with deviations driven mainly by vascular (n=13), hematologic (n=11), renal (n=7), or infectious (n=5) events 2
Carboplatin Substitution
- Do not substitute carboplatin for cisplatin in NSGCT—multiple randomized trials demonstrate inferior outcomes 5, 6
- Carboplatin-based regimens (CEB) showed significantly higher relapse rates (32% vs 13%) and more deaths compared to cisplatin-based regimens (PEB) 6
- Complete response rates were lower with carboplatin (87.3% vs 94.4%, P=0.009) 5
Postchemotherapy Management
- Complete surgical resection of residual disease is essential—30% of nonseminoma patients have teratoma or viable GCT at postchemotherapy surgery 2, 3
- Postchemotherapy RPLND should use full bilateral template dissection, not limited "pick-up" lymphadenectomy 1
Toxicity Monitoring
Expected Toxicities with EP
- Febrile neutropenia occurs in 16% of patients 2
- Thromboembolic events occur in 8.9% of patients 1, 2
- Grade II or greater neurologic, renal, or pulmonary toxicity is rare with EP alone 7
- Treatment-related mortality is approximately 0.1% 2