A 52-year-old woman with stage IIIB cervical cancer (parametrial involvement, no distant metastases) is deemed unfit for surgery due to comorbidities. She has normal renal function and good performance status. What is the drug of choice for concurrent chemoradiation therapy?

Explanation

## Concurrent Chemoradiation for Locally Advanced Cervical Cancer **Key Point:** Cisplatin is the drug of choice for concurrent chemoradiation in locally advanced cervical cancer (stage IIB–IVA). Weekly cisplatin at 40 mg/m² is the standard regimen that balances efficacy and tolerability during pelvic radiation. ### Why Cisplatin? **High-Yield:** Cisplatin is the only chemotherapeutic agent with proven survival benefit when combined with pelvic radiation for cervical cancer: - Radiosensitizing effect: enhances DNA damage from radiation - Absolute 5-year overall survival improvement of ~10–12% vs. radiation alone (meta-analyses) - Supported by GOG, EORTC, and FIGO guidelines - Landmark trials: GOG 85, GOG 120, GOG 165 ### Dosing for Concurrent Chemoradiation **Clinical Pearl:** The standard regimen is: - **Cisplatin 40 mg/m² IV weekly** (days 1, 8, 15, 22, 29 during pelvic radiation) - Total of 5 doses over 5–6 weeks of external beam radiation therapy (EBRT) - Followed by brachytherapy This dose is lower than neoadjuvant chemotherapy (75 mg/m²) to minimize acute toxicity during concurrent radiation. ### Mechanism of Radiosensitization ```mermaid flowchart TD A[Cisplatin + Radiation]:::action --> B[DNA Cross-linking]:::outcome B --> C[Inhibition of DNA Repair]:::outcome C --> D[Enhanced Cell Death]:::outcome D --> E[Improved Local Control & OS]:::outcome ``` ### Comparison with Alternatives | Agent | Role in Cervical Cancer | Evidence | Limitation | |-------|-------------------------|----------|----------| | **Cisplatin 40 mg/m² weekly** | **Concurrent CCRT** | **Level 1A (RCTs)** | **STANDARD OF CARE** | | Carboplatin weekly | Cisplatin-ineligible (renal dysfunction, neuropathy) | Limited data; inferior efficacy | Not first-line; requires renal impairment | | Paclitaxel weekly | Recurrent/metastatic disease | No role in CCRT | Not radiosensitizing; no survival benefit | | 5-FU continuous infusion | Historical (older regimens); now obsolete | Inferior to cisplatin | Replaced by cisplatin-based CCRT | **Mnemonic:** **CCRT-CC** = **C**oncurrent **C**hemoradiation **T**herapy for **C**ervical **C**ancer = **Cisplatin 40 mg/m² weekly**. ### Eligibility & Contraindications **Warning:** Cisplatin requires: - Normal renal function (creatinine clearance ≥60 mL/min) - Adequate hydration and antiemetic prophylaxis - Monitoring for ototoxicity and peripheral neuropathy If cisplatin is contraindicated (severe renal impairment, severe hearing loss), carboplatin may be considered, but efficacy is less robust. [cite:FIGO Guidelines 2019; Gynecologic Oncology Society Recommendations]