Nigro Protocol consists of radiation therapy combined with 5-FU and mitomycin-C. It is the standard first step of treatment for most people diagnosed with anal cancer in stages I through III, specifically for squamous cell carcinoma.


In 1974, Dr. Norman Nigro developed what was initially supposed to be a 'first step' therapy for invasive anal carcinoma that was designed to help shrink tumors before surgery. Instead, and to their surprise, Dr. Nigro and his colleagues observed complete tumor regression in some patients using this therapy protocol. This protocol consisted of treatment with fluorouracil (5-FU)-based chemotherapy administered concurrently with radiation and the addition of either mitomycin or porfiromycin chemotherapy. Their observations suggested that it might be possible to cure anal carcinoma without surgery and its associated after effects.

Prior to the 1970s, individuals diagnosed with invasive anal carcinoma were typically treated with an abdominoperineal resection (removal of the anus, rectum and part of the large intestine), no matter the stage of their cancer. Since Dr. Nigro’s discovery, the standard treatment for most anal carcinoma has shifted away from invasive operations.

Dr. Nigro’s chemoradiation procedure became known as the Nigro Protocol.

Nigro Protocol Treatment

Radiation therapy, doctor with patient

Today, the Nigro Protocol consists of radiation therapy combined with 5-FU and mitomycin-C. 5-FU is usually administered through an IV over the course of four to five days at the beginning of treatment and repeated after four to six weeks. Mitomycin is also given as an IV injection, usually at the start of radiation treatment and then again towards the end, about four to six weeks later. This 'first step' is still the standard of care for most people diagnosed with anal cancer in stages I through III. The National Comprehensive Cancer Network (NCCN) also states that a combination of mitomycin and capecitabine plus radiation therapy can also be used as an alternative to the mitomycin and 5-FU combination.

The standard protocol for people diagnosed with stage IV anal cancer has also seen limited advancement. Cisplatin was first created in the mid 19th century and 5-FU in the 1950s. This combination has existed as the initial treatment protocol for anal cancer since the 1970s.

Side Effects

Despite the success of chemoradiation therapy for survival and overall prognosis, significant side effects are still reported:

  • During treatment complaints commonly include, but are not limited to, diarrhea, anaemia, dermatitis (red, itchy, swollen skin), leukopenia (a shortage of white blood cells) and thrombocytopenia (low platelet count).
  • After treatment thrivers report bowel management challenges, vaginal stenosis, anal stenosis, erectile dysfunction and urinary dysfunction.

Please note that we have separated these side effects into 'during treatment' and 'after treatment' because certain side effects are more common at these two stages of treatment. However, it is still possible to experience some or all (or none) of them throughout treatment or at different points in time than we have explained here.

For a more in-depth explanation of the side effects you may experience, and advice on how to manage them, please see our Radiation and Chemotherapy pages.

Today, the Anal Cancer Foundation is working to help the field move beyond the Nigro Protocol and stage IV standard treatment. We do this by actively seeking out and funding research into treatments that are as effective and with fewer side effects. See our Accomplishments and Research Roadmap pages for more information about how we are changing this for anal cancer thrivers.

Looking for someone to talk to about your anal cancer diagnosis? We are here to help. The Peer to Peer Support Program is a free service provided by the Anal Cancer Foundation that matches anal cancer thrivers (our word for survivors) and caregivers with thriver volunteers and caregiver volunteers.

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