A 38-year-old woman presents with stage IB cervical carcinoma (tumor size 4 cm) confirmed on biopsy. She is otherwise healthy with normal renal and hepatic function. What is the drug of choice for concurrent chemoradiation therapy in this patient?

Explanation

## Cervical Carcinoma Chemotherapy in Concurrent Chemoradiation ### Standard of Care for Locally Advanced Cervical Cancer **Key Point:** Cisplatin is the gold-standard chemosensitizing agent used concurrently with external beam radiotherapy (EBRT) and brachytherapy in locally advanced cervical carcinoma (stages IB2–IVA). ### Evidence Base Multiple randomized trials (GOG-120, SWOG-8797, RTOG-90-01) demonstrated that concurrent cisplatin-based chemoradiation improves overall survival and disease-free survival by 10–15% compared to radiation alone in locally advanced cervical cancer. ### Cisplatin Dosing in Cervical Cancer - **Standard regimen:** 40 mg/m² IV weekly × 5–6 weeks concurrent with EBRT - **Alternative:** 75 mg/m² IV every 3 weeks (less commonly used due to toxicity) - **Mechanism:** Platinum-DNA crosslinking enhances radiosensitivity; acts as a radiation sensitizer ### Why Cisplatin Over Alternatives | Feature | Cisplatin | Carboplatin | Paclitaxel | 5-FU | |---------|-----------|-------------|-----------|-------| | **Radiosensitizer** | Yes (proven) | No | No | Weak | | **Level of evidence** | Phase III RCTs | Limited data | Investigational | Inferior | | **Concurrent EBRT safety** | Established | Not standard | Not standard | Not standard | | **Survival benefit** | +10–15% | Unknown | Unknown | Inferior | **High-Yield:** GOG-120 and SWOG-8797 trials established cisplatin as the standard; no other agent has equivalent level-1 evidence for concurrent chemoradiation in cervical cancer. ### Clinical Considerations **Clinical Pearl:** Weekly cisplatin 40 mg/m² is preferred over higher-dose regimens because it provides better tolerability during concurrent radiation without compromising efficacy. Renal function and hearing must be monitored. **Warning:** Carboplatin is NOT a substitute for cisplatin in concurrent chemoradiation—it lacks the proven radiosensitizing effect and has not been validated in phase III trials for this indication. ### Contraindications to Cisplatin - Severe renal impairment (CrCl < 60 mL/min) - Significant hearing loss or neuropathy - Uncontrolled nausea/vomiting In such cases, consider alternative regimens (e.g., carboplatin + paclitaxel) or radiation alone, but these are not standard of care. [cite:Harrison 21e Ch 107]