Can carboplatin (carboplatin) and etoposide (etoposide) be used as an alternative to the cisplatin (cisplatin) and etoposide (PE) regimen?

Carboplatin-Etoposide (CE) Regimen as an Alternative to Cisplatin-Etoposide (PE) in Small Cell Lung Cancer

Yes, carboplatin and etoposide can be referred to as the CE regimen and is an established alternative to the cisplatin-etoposide (PE) regimen, particularly for patients with contraindications to cisplatin. 1

Evidence Supporting CE as an Alternative to PE

Efficacy Comparison

• The American Society of Clinical Oncology (ASCO) 2023 guidelines strongly recommend carboplatin-etoposide as an alternative systemic therapy for patients with limited-stage small cell lung cancer (LS-SCLC) who have contraindications to cisplatin 1

• A randomized trial directly comparing PE to CE in patients with both limited-stage and extensive-stage SCLC showed comparable response rates:

  • For LS-SCLC: 76% for PE and 86% for CE
  • No clinically relevant differences in time to progression (8.4 vs 8.6 months) or overall survival (12.5 vs 11.8 months) 1

• The COCIS meta-analysis of 663 patients from four trials comparing cisplatin to carboplatin-based therapy showed no significant differences in:

  • Response rate (67% vs 66%)
  • Median progression-free survival (5.5 vs 5.3 months)
  • Median overall survival (9.6 vs 9.4 months) 1

Toxicity Differences

• Carboplatin-based regimens result in more myelosuppression (bone marrow suppression) 1
• Cisplatin causes more nausea, vomiting, neurotoxicity, and nephrotoxicity 1
• The FDA label for cisplatin lists hypersensitivity as a contraindication, with nephrotoxicity, neuropathy, and ototoxicity as black box warnings 1

Clinical Applications

When to Use CE Instead of PE

1. Contraindications to cisplatin:

   • Renal impairment
   • Pre-existing peripheral neuropathy
   • Hearing loss/ototoxicity
   • History of severe cisplatin-induced nausea/vomiting
   • Hypersensitivity to cisplatin 1, 2

2. Patient factors favoring carboplatin:

   • Elderly patients
   • Poor performance status
   • Comorbidities that increase risk of cisplatin toxicity 1

Standard Dosing for CE Regimen

• Carboplatin AUC 5-6 intravenously on day 1
• Etoposide 100-120 mg/m² intravenously on days 1-3
• Repeated every 3 weeks for 4 cycles 1, 2

Important Considerations

Monitoring and Management

• More frequent complete blood count monitoring may be needed with CE due to higher risk of myelosuppression
• Consider prophylactic growth factor support in high-risk patients
• Monitor for thrombocytopenia which is more common with carboplatin 1, 2

Common Pitfalls

1. Underdosing: Maintaining dose intensity is important, especially during the first two cycles 1
2. Overextending treatment: No evidence supports extending beyond 4 cycles of chemotherapy 1
3. Inappropriate substitution: While CE is an acceptable alternative, PE remains the preferred regimen for patients who can tolerate cisplatin, particularly in the limited-stage setting 1

Evolution of Treatment Standards

The NCCN guidelines have evolved to include carboplatin-etoposide as a standard option, particularly when combined with immunotherapy for extensive-stage disease. For limited-stage disease, cisplatin-etoposide remains the preferred regimen when patients can tolerate it, but carboplatin substitution is acceptable when necessary 1.

In conclusion, while cisplatin-etoposide (PE) remains the preferred regimen for SCLC when patients can tolerate it, carboplatin-etoposide (CE) is an established and effective alternative with comparable efficacy but a different toxicity profile.