What is the Nigro protocol (chemoradiation therapy regimen) for treating anal cancer?

From the Guidelines

The Nigro protocol is a standard chemoradiation therapy regimen for treating anal cancer that combines radiation therapy with concurrent chemotherapy, and the most recent and highest quality study recommends mitomycin C (MMC) with a fluoropyrimidine (FU or capecitabine) as the radiosensitizing component of chemoradiation for anal cancer 1. The protocol typically consists of 5-fluorouracil (5-FU) administered as a continuous infusion at 1,000 mg/m²/day for 4 days during weeks 1 and 5 of radiation therapy, along with mitomycin C given as a bolus injection at 10-15 mg/m² on day 1 of treatment.

• Radiation therapy is delivered to the primary tumor and regional lymph nodes at a total dose of 45-54 Gy, typically given in 1.8-2 Gy fractions over 5-6 weeks.
• For patients who cannot tolerate mitomycin C, cisplatin at 75-100 mg/m² on days 1 and 29 may be substituted.
• Treatment requires careful monitoring for side effects including myelosuppression, radiation dermatitis, and gastrointestinal toxicity, with supportive care measures implemented as needed. This approach has become the standard of care for anal cancer because it allows for organ preservation while achieving high rates of local control and cure, avoiding the need for permanent colostomy in most patients, as supported by studies such as the UKCCCR Anal Cancer Trial I phase III randomized clinical trial 1. The protocol works by using radiation to directly damage tumor DNA while chemotherapy acts as a radiosensitizer, enhancing the effectiveness of radiation therapy against cancer cells.
• The recommended dosing and schedules for the chemotherapy options included in the Nigro protocol are outlined in the ASCO guideline, with mitomycin C and 5-FU being the preferred combination 1.
• The use of capecitabine as an alternative to 5-FU has also been explored, with studies showing comparable outcomes 1.
• Cisplatin with 5-FU is also an accepted alternative, with the UK ACT II trial demonstrating non-inferiority compared to mitomycin C and 5-FU 1. The Nigro protocol has been widely adopted and is considered the standard of care for anal cancer, with ongoing research aimed at optimizing treatment outcomes and minimizing toxicity, as seen in the 2025 ASCO guideline 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Mitomycin should be given intravenously only, using care to avoid extravasation of the compound. After full hematological recovery (see guide to dosage adjustment) from any previous chemotherapy, the following dosage schedule may be used at 6- to 8-week intervals: 20 mg/m2 intravenously as a single dose via a functioning intravenous catheter When mitomycin is used in combination with other myelosuppressive agents, the doses should be adjusted accordingly.

The Nigro protocol is a chemoradiation therapy regimen that typically consists of:

• Mitomycin-C (IV): 10-15 mg/m2 on days 1 and 29
• 5-Fluorouracil (5-FU): 1000 mg/m2 per day as a continuous infusion on days 1-4 and 29-32
• Radiation therapy: 30-40 Gy in 15-20 fractions over 3-4 weeks

Key points:

• The Nigro protocol is used to treat anal cancer
• The regimen combines chemotherapy (mitomycin-C and 5-FU) with radiation therapy 2

From the Research

Nigro Protocol Overview

• The Nigro protocol is a chemoradiation therapy regimen used to treat anal cancer, specifically squamous cell carcinomas 3.
• This protocol typically involves the use of mitomycin C and 5-Fluorouracil (5-FU) in combination with radiation therapy 4, 5.

Treatment Components

• The treatment regimen consists of concurrent chemoradiation therapy, where chemotherapy is administered alongside radiation therapy 4, 6, 5.
• The chemotherapy component typically includes mitomycin C and 5-FU, which are given concurrently with radiation therapy 4, 5.
• Radiation therapy is delivered to the anal region, perineum, and inguinal nodes, with a total dose of 50-60 Gy 4, 6.

Efficacy and Outcomes

• The Nigro protocol has been shown to be effective in treating anal cancer, with primary tumor control rates ranging from 68% to 93% 4, 5.
• The use of mitomycin C and 5-FU in combination with radiation therapy has been associated with improved survival rates and preservation of anorectal function 4, 5.
• A study comparing the Nigro protocol to radiation therapy alone found that the combined modality approach resulted in improved primary tumor control and reduced colostomy rates 4.

Toxicity and Side Effects

• The Nigro protocol can be associated with significant toxicity, including acute hematologic and enterocolic toxicity, as well as late toxicity requiring surgical intervention 4, 5.
• The use of intensity-modulated radiation therapy (IMRT) has been explored as a means of reducing treatment-related morbidity and improving disease-related outcomes 7.