Concurrent Cisplatin and Radiotherapy for Cervical Cancer

Concurrent cisplatin and radiotherapy for cervical cancer involves weekly low-dose cisplatin during external pelvic radiotherapy and/or brachytherapy. Cisplatin's radiosensitizing effect aims to increase radiation's activity against the tumor.

Concurrent cisplatin and radiotherapy is standard treatment for locally advanced cervical cancer. It may be used with curative intent or as postoperative adjuvant treatment.

Treatment Indications

Locally Advanced Cervical Cancer

• FIGO Stage IB3 (≥4 cm)
• Stage II (extension from the cervix into the parametrial tissues)
• Stage III (pelvic wall involvement, lower 1/3 of the vagina or hydronephrosis)
• Stage IVA (bladder or rectal invasion)
• Positive pelvic or para-aortic lymph nodes

Postoperative Adjuvant Treatment

When high-risk features are present after surgery, such as:

• Positive surgical margins,
• Lymph node metastasis,
• Deep stromal invasion + vascular invasion

Cisplatin may be given with adjuvant radiotherapy.

Treatment Goals

• Improve local control,
• Increase tumor cell sensitivity to radiation,
• Reduce tumor burden, including lymph node metastases,
• Extend survival and reduce recurrence risk.

How Does This Treatment Work?

Radiotherapy:

• High-energy ionizing radiation damages tumor cell DNA directly or through free radicals.
• If damage cannot be repaired, the cell cycle stops and apoptosis (programmed cell death) follows.
• Radiotherapy provides local control in the targeted area, such as the cervix, parametrial tissues and pelvic lymph nodes.

Cisplatin (Radiosensitizing Chemotherapy):

• Cisplatin forms DNA crosslinks, blocking DNA replication and repair.
• Cells become unable to repair radiation-induced DNA damage.
• This increases radiosensitivity and makes tumor cell killing more effective.
• Even at low systemic doses, cisplatin may also act against micrometastases.

Synergy:

• Concurrent administration improves local control compared with radiotherapy alone,
• Reduces recurrence and extends survival.
• It has therefore become standard for locally advanced cervical cancer.

Dosage

Cisplatin

• Dose: 40 mg/m² (usually capped at a maximum of 70 mg)
• Frequency: 1 time weekly (one dose per week)
• Duration: Usually 5 to 6 weeks, throughout radiotherapy
• Administration: IV (intravenous), usually over 30–60 minutes
• Hydration: Generous fluids before and after treatment are required because of nephrotoxicity risk.

Radiotherapy (External Beam and Brachytherapy)

1. External Beam Pelvic Radiotherapy (EBRT):

• Dose: 45–50.4 Gy
• Fractions: 1 daily, 5 days per week
• Total Duration: Approximately 5 weeks

2. Brachytherapy (Internal Radiotherapy):

• Dose: Usually 6–7 Gy x 3–5 fractions
• Starting Time: May begin during the final 2 weeks of external RT
• Aim: Deliver a high local dose to the primary cervical tumor

Special Considerations

• Kidney Function (Nephrotoxicity Risk): Cisplatin is cleared through the kidneys and carries a high nephrotoxicity risk. It is contraindicated with creatinine clearance < 50 mL/min. IV hydration before and after treatment is mandatory. Monitor electrolytes (Mg, K, Na) regularly.
• Hematological Toxicities: Leukopenia, neutropenia, anemia and thrombocytopenia may occur. Check complete blood counts weekly; reduce or delay cisplatin if needed.
• Gastrointestinal Toxicities: Nausea, vomiting, diarrhea and mucositis are common. Antiemetic prophylaxis is mandatory. Pelvic radiation may cause enteritis, colitis or diarrhea, increasing dehydration and electrolyte loss risk.
• Radiation Toxicities:Radiation cystitis and enteritis are among the commonest local toxicities. Prolonged radiotherapy may cause rectal bleeding, burning urination and urinary frequency. Radiation dermatitis may occur, particularly in the vulvar/perineal area.
• Performance Status and Nutrition: Patients with ECOG performance status ≥2 or poor general condition may not tolerate this regimen. Weight loss, appetite loss and nutritional problems during treatment require supportive care.
• Pregnancy: Both radiation and cisplatin cause fetal toxicity. Exclude pregnancy before treatment in patients of reproductive age and ensure effective contraception.
• Neurotoxicity and Ototoxicity (Cisplatin-Related): Long-term use may cause sensory loss or tinnitus. Particular caution is needed in older patients.
• Treatment Delays:Total radiotherapy duration must not exceed 56 days; GOG protocols associate delays with reduced survival. Avoid prolongation from scheduling problems, hematological toxicity interruptions or similar causes.

Side Effects

Concurrent cisplatin and radiotherapy for cervical cancer causes adverse effects from both radiation and chemotherapy. These mainly affect the hematological, gastrointestinal and renal systems. Major side effects and their frequencies are listed below:

• Leukopenia (reduced white blood cells): 60–70%
• Neutropenia (reduced immune-defense cells): 40–60%
• Anemia: 40–60%
• Thrombocytopenia (reduced platelets): 20–30%
• Nausea / Vomiting: 60–80%
• Diarrhea (radiation enteritis-related): 40–60%
• Mucositis (oral and vaginal burning/sores): 30–40%
• Loss of appetite, weight loss: 30–40%
• Fatigue: 50–70%
• Kidney dysfunction (nephrotoxicity): 10–25%
• Hypomagnesemia / electrolyte imbalance: 20–30%
• Radiation cystitis (burning urination, urgency): 25–40%
• Radiation dermatitis (redness, tenderness): 30–50%
• Neuropathy (sensory loss, tingling): 5–10%
• Ototoxicity (tinnitus, hearing loss): <5%