A 38-year-old woman with recurrent cervical cancer (metastatic to para-aortic lymph nodes) after prior chemoradiation is being considered for palliative chemotherapy. Which regimen is the preferred first-line option for recurrent/metastatic cervical cancer?

Explanation

## First-Line Chemotherapy for Recurrent/Metastatic Cervical Cancer **Key Point:** Cisplatin + paclitaxel + bevacizumab (anti-VEGF monoclonal antibody) is the gold-standard first-line regimen for recurrent or metastatic cervical cancer, based on the GOG 240 trial. ### GOG 240 Trial Evidence (2013) This landmark Phase III trial compared: - **Arm 1:** Cisplatin + paclitaxel + bevacizumab ← **SUPERIOR** - **Arm 2:** Cisplatin + paclitaxel (without bevacizumab) - **Arm 3:** Topotecan + cisplatin - **Arm 4:** Topotecan + cisplatin + bevacizumab | Outcome | Cisplatin + Paclitaxel + Bevacizumab | Cisplatin + Paclitaxel Alone | |---------|---------------------------------------|-----------------------------| | Median OS | 17.0 months | 12.9 months | | Median PFS | 8.2 months | 5.9 months | | ORR | 48% | 36% | | Grade 3–4 toxicity | Higher (manageable) | Lower | **High-Yield:** The addition of bevacizumab to chemotherapy improved overall survival by 4.1 months (absolute benefit), making it the standard of care for fit patients with recurrent/metastatic cervical cancer. ### Mechanism of Bevacizumab - Monoclonal antibody against vascular endothelial growth factor (VEGF) - Inhibits tumor angiogenesis - Synergizes with platinum-taxane chemotherapy - Reduces tumor vascularity and improves drug delivery ### Dosing Schedule - **Cisplatin:** 75 mg/m² IV on day 1 - **Paclitaxel:** 160 mg/m² IV on day 1 - **Bevacizumab:** 15 mg/kg IV on day 1 - Repeat every 21 days for 6 cycles (or until progression/toxicity) ### Clinical Pearl Bevacizumab is contraindicated in patients with: - Uncontrolled hypertension - Recent thromboembolic events - Active bleeding or coagulopathy - Renal impairment (creatinine >1.5× ULN) - Pregnancy or lactation For patients unfit for cisplatin (renal impairment, hearing loss, neuropathy), **carboplatin + paclitaxel + bevacizumab** is an acceptable alternative, though cisplatin is preferred when tolerable. **Warning:** Do NOT use bevacizumab monotherapy or topotecan alone — these have inferior outcomes compared to the triplet regimen in GOG 240. [cite:Tewari et al., NEJM 2014; NCCN Cervical Cancer Guidelines 2023]