Are carboplatin or etoposide (chemotherapy agents) radiosensitizing?

Radiosensitizing Properties of Carboplatin and Etoposide

Yes, both etoposide and carboplatin have radiosensitizing properties, with etoposide being the more established radiosensitizer when combined with platinum agents in concurrent chemoradiotherapy regimens.

Etoposide as a Radiosensitizer

Etoposide combined with cisplatin represents the gold standard radiosensitizing chemotherapy regimen for concurrent chemoradiotherapy in limited-stage small cell lung cancer (LS-SCLC). 1 The combination has been used as the backbone in the majority of trials evaluating concurrent chemoradiotherapy, demonstrating high-quality evidence for its efficacy when administered with radiation. 1

• In stage III non-small cell lung cancer (NSCLC), the ESMO guidelines explicitly state that cisplatin may be combined with etoposide, vinorelbine, or other vinca alkaloids for concurrent radiotherapy. 1
• The radiosensitizing effect of etoposide is well-established when used in platinum-based doublets during concurrent radiation therapy. 1

Carboplatin as a Radiosensitizer

The evidence for carboplatin as a single-agent radiosensitizer is weak and not firmly established, though it demonstrates radiosensitizing properties in combination regimens. 1

Evidence Against Single-Agent Carboplatin:

• ESMO guidelines explicitly state: "There are no firm conclusions supporting single agent carboplatin as a radiation sensitiser." 1
• Single-agent carboplatin failed to improve survival when given concurrently with radiotherapy in two prospective randomized trials in stage III NSCLC. 1

Evidence Supporting Carboplatin in Combination:

• Carboplatin combined with etoposide may be offered as systemic therapy concurrent with radiation for patients with LS-SCLC who have contraindications to cisplatin. 1 This recommendation carries strong support despite low-quality evidence. 1
• Preclinical data demonstrates carboplatin can act as a potentiator of radiation therapy through radiosensitization of hypoxic cells (enhancement ratio of 1.8) and inhibition of recovery from radiation-induced damage. 2
• In clinical practice, carboplatin plus etoposide with concurrent radiotherapy showed comparable efficacy to cisplatin-based regimens in LS-SCLC, with no significant differences in response rates (86% vs 76%) or survival outcomes. 1

Clinical Context and Practical Application

When concurrent chemoradiotherapy is indicated, the choice should follow this algorithm:

1. First-line: Cisplatin plus etoposide with concurrent radiation (high-quality evidence, strong recommendation). 1

2. Alternative for cisplatin-intolerant patients: Carboplatin plus etoposide with concurrent radiation (acceptable alternative with similar efficacy but more myelosuppression). 1

3. Avoid: Single-agent carboplatin as a radiosensitizer (insufficient evidence of benefit). 1

Important Caveats:

• The radiosensitizing benefit of carboplatin appears dependent on combination with other agents, particularly etoposide, rather than as monotherapy. 1, 2
• Carboplatin-etoposide regimens result in more myelosuppression compared to cisplatin-based therapy, while cisplatin causes more nausea, vomiting, neurotoxicity, and nephrotoxicity. 1
• In neoadjuvant settings for locally advanced NSCLC, carboplatin with etoposide and concurrent radiotherapy demonstrated feasibility without increased radiation-related toxicity. 3