Topical chemotherapy
Everything to know about topical chemotherapy
Topical chemotherapy is a complementary therapeutic approach for treating superficial conjunctival neoplasms—cases in which tumor cells are confined to the epithelium (also known as tumors in situ). This method, typically offered after surgery, involves the direct application of cytotoxic agents to the ocular surface to eliminate residual tumor cells.
Adjuvant treatment (post-surgical)
Topical chemotherapy is used as an adjuvant therapy after surgical excision to reduce the risk of local recurrence of malignant conjunctival tumors such as carcinoma in situ and melanoma in situ. This approach can prevent the need for wide resections by targeting microscopic residual tumor cells that surgery alone cannot completely remove.
Neoadjuvant treatment (pre-surgical)
In selected cases, topical chemotherapy may be used as a first-line treatment, particularly in situations involving:
- Extensive tumors: for large lesions where immediate surgery would be disfiguring, neoadjuvant therapy can reduce tumor volume and allow for more conservative surgical removal later.
- Difficult locations: tumors involving the canthi, lacrimal puncta, or extending onto the eyelids may benefit from initial chemical cytoreduction.
- Multifocal tumors: multiple lesions or extensive conjunctival intraepithelial neoplasia may justify initial topical treatment.
Mitomycin C (MMC)
Mitomycin C is the gold standard for topical ocular chemotherapy. It is an alkylating antitumor antibiotic that cross-links DNA strands, inhibiting cell replication. It selectively targets rapidly dividing cells, which are characteristic of epithelial conjunctival neoplasms.
5-Fluorouracil (5-FU)
5-FU is an alternative to Mitomycin C. It is a pyrimidine antimetabolite that inhibits thymidylate synthase, a key enzyme in DNA synthesis. This causes nucleotide imbalance and blocks cell cycle progression.
- Concentration
- Dosing
- Cycle duration
- Days off
- Number of cycles
Mitomycin C (MMC)
- Concentration 0.02% to 0.04%
- Dosing 1 drop 4 times a day
- Cycle duration 2 weeks
- Days off 7
- Number of cycles 2 cycles
5-Fluorouracil (5-FU)
- Concentration 1%
- Dosing 1 drop 4 times a day
- Cycle duration 1 week
- Days off 21
- Number of cycles 3 to 6 cycles
Cyclic treatment enhances efficacy while reducing toxicity:
- Active phase: during the treatment period, dividing tumor cells are destroyed by the cytotoxic agent. Repeated application maintains a therapeutic drug concentration locally.
- Rest phase: the drug-free interval allows regeneration of healthy conjunctival epithelium, while the residual drug activity continues to affect remaining tumor cells due to tissue persistence.
Preparation and storage
These chemotherapy eye drops are not available at retail pharmacies and must be compounded at hospital pharmacies. They require refrigeration and protection from light due to limited stability after reconstitution.
Instillation technique
Preparing:
- Wash hands thoroughly
- Sit or lie down with head tilted slightly backward
- Clean the eye with sterile saline if needed
Instillation:
- Gently pull down the lower eyelid to form a conjunctival sac
- Instill one drop into the conjunctival fornix, avoiding contact between bottle tip and eye
- Close eyes gently for 1–2 minutes
- Wipe off any excess with a sterile gauze pad
Post-instillation precautions:
- Avoid rubbing the eye for at least 30 minutes
- Use an eye patch if needed
- Wash hands immediately after application
Mild inflammation with conjunctival redness is common and indicates treatment activity. However, chemotherapy toxicity—depending on the drug and dosage—can lead to:
- Keratitis or severe corneal/conjunctival ulceration (causing pain and light sensitivity)
- Severe dry eye syndrome
- Excessive scarring with symblepharon formation
Management: any significant side effect warrants prompt ophthalmologic evaluation, and may require dosage adjustment or discontinuation of treatment.
Topical chemotherapy requires close medical supervision to assess treatment tolerance. Ophthalmologic follow-up is essential before and between each treatment cycle to detect complications that may necessitate dose adjustment or stopping therapy. The treatment’s effectiveness is evaluated later by the referring ocular oncologist.