Chemotherapy and Other Systemic Therapies for Rectal Cancer

MSK is a leader in developing new systemic therapies for treating rectal cancer.
MSK clinical nurse Megan McCue is in an infusion suite at the David H. Koch Center for Cancer Care, preparing treatment.
Clinical nurse Megan McCue in is at the David H. Koch Center for Cancer Care. 
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Overview

Rectal cancer chemotherapy (chemo), targeted therapy, and immunotherapy are called systemic therapies. They travel through the bloodstream to treat cancer cells anywhere in the body.

Rectal cancer treatment depends on the cancer’s stage, location, and the tumor’s traits. Your care team may recommend systemic therapies to treat the cancer. 

You may have neoadjuvant (NEE-oh-A-joo-vant) therapy, which is systemic therapy you get before rectal cancer surgery. Neoadjuvant therapy shrinks tumors so they’re easier to remove during surgery.

You may have adjuvant (A-joo-vunt) therapy, which is systemic therapy you get after rectal cancer surgery. It’s used to kill any cancer cells that may be left in your rectum or the rest of your body. 
 

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Chemotherapy for rectal cancer

What is chemotherapy (chemo)?

Chemotherapy (chemo) is a treatment that uses strong medicine to stop or slow cancer cells from growing. Chemo can be taken by mouth as pills. It also can be injected (put) through a drip into your vein. The medicines travel in your bloodstream to kill cancer cells anywhere in the body.   

In general, these medicines treat rectal cancer by affecting how cancer cells grow and spread. 

There are many types of chemotherapy medicines, and they do not work in the same way. They have different doses and schedules. Some are used alone, others along with other medicines. There also are differences in how well chemo medicines work.  

Chemotherapy given along with radiation is called chemoradiation. 

Your care team will talk with you about the best options. 

Chemotherapy medicines and regimens

If chemotherapy is a part of your treatment, your medical oncologist (cancer doctor) will recommend a chemotherapy plan. It’s also called a chemotherapy regimen (REH-jih-men).  

A treatment plan tells you important details, including: 

  • Which medicines you’ll get.
  • The order in which you’ll get them.
  • The dose (amount) of each drug.
  • How often and how long you’ll need chemotherapy. 

Chemotherapy before rectal cancer surgery

MSK is a leader in developing total neoadjuvant therapy for rectal cancer. This method uses chemotherapy along with radiation therapy.  

You’ll either have chemoradiation and then chemotherapy for 3 to 4 months, or chemotherapy followed by chemoradiation. 

Your care team may recommend this approach for cancer that spread past the rectum, or is close to the anus.  

Total neoadjuvant therapy shrinks the tumor with less harm to the anal sphincter muscle. That means you still can go to the bathroom normally. 

Rectal cancer may go away for almost half of the people who were treated with total neoadjuvant therapy. If there’s no sign of rectal cancer, you may not need surgery. Your colorectal surgeon will check your rectum every 3 to 4 months with flexible sigmoidoscopy and imaging tests. If there’s a sign of rectal cancer, you’ll have surgery.  

Chemotherapy after rectal cancer surgery

Adjuvant therapy regimens include: 

  • FOLFOX
  • CAPOX
  • 5-FU only
  • Capecitabine only 

Hepatic artery infusion chemotherapy for rectal cancer that has spread to the liver

Hepatic artery infusion (HAI) is a kind of chemotherapy.  

Hepatic (heh-PA-tik) means the liver. Rectal cancer most often spreads to the liver through the bloodstream.  

HAI delivers chemotherapy drugs right to the liver. The drugs go into the liver through the hepatic artery, which supplies blood to the liver. 

The drugs go through a tiny pump that’s implanted (put) under the skin in the lower abdomen (belly). HAI delivers treatment right to the tumor, which limits side effects. It can shrink tumors so they can be removed with surgery. 

MSK gastrointestinal oncologist Dr. Deb Schrag is in a hallway at MSK in New York City.
My hope is this treatment approach will give people with rectal cancer a new option. At MSK, our mission is to keep pushing the boundaries to make meaningful differences for our patients.
Gastrointestinal oncologist Dr. Deb Schrag led MSK research on treating locally advanced rectal cancer safely without radiation therapy.
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Your care team will make a treatment plan. It’s based on the type of cancer you have and how far the cancer has spread:
Chemotherapy for early-stage rectal cancer
Your care team may recommend chemotherapy before or after rectal cancer surgery. 
Chemotherapy for early-stage rectal cancer

People with stages 0, 1, or 2 rectal cancers may have surgery, chemotherapy, or radiation therapy.  

When you have chemo and radiation together, it’s called chemoradiation. There are 2 ways to have chemoradiation: 

  • You have chemo in the form of pills (capecitabine) taken 2 times a day on the days you have radiation.
  • You have chemo in the form of intravenous (IV) 5-fluorouracil. It’s given through a small pump on the days you have radiation, from Monday to Friday. 

Your doctor will decide which order you have these treatments: 

  • Treatment may start with chemoradiation, followed by chemo for 3 to 4 months.
  • Treatment may start with chemo for 3 to 4 months, followed by chemoradiation. 

We may recommend chemotherapy for early-stage rectal cancer because chemo: 

  • Raises the chance your surgeon will remove all of the cancer.
  • Shrinks the tumor so it’s easier to remove during surgery.
  • Kills rectal cancer cells that remain after surgery, so there’s less chance the cancer will come back. 
Chemotherapy regimens

Some of the drugs used in chemotherapy regimens for rectal cancer are: 

  • Fluorouracil (5-FU)
  • Capecitabine
  • Oxaliplatin
  • Leucovorin 
Up Next
Chemotherapy for later-stage and metastatic rectal cancer
Chemotherapy for early-stage rectal cancer

People with stages 0, 1, or 2 rectal cancers may have surgery, chemotherapy, or radiation therapy.  

When you have chemo and radiation together, it’s called chemoradiation. There are 2 ways to have chemoradiation: 

  • You have chemo in the form of pills (capecitabine) taken 2 times a day on the days you have radiation.
  • You have chemo in the form of intravenous (IV) 5-fluorouracil. It’s given through a small pump on the days you have radiation, from Monday to Friday. 

Your doctor will decide which order you have these treatments: 

  • Treatment may start with chemoradiation, followed by chemo for 3 to 4 months.
  • Treatment may start with chemo for 3 to 4 months, followed by chemoradiation. 

We may recommend chemotherapy for early-stage rectal cancer because chemo: 

  • Raises the chance your surgeon will remove all of the cancer.
  • Shrinks the tumor so it’s easier to remove during surgery.
  • Kills rectal cancer cells that remain after surgery, so there’s less chance the cancer will come back. 
Chemotherapy regimens

Some of the drugs used in chemotherapy regimens for rectal cancer are: 

  • Fluorouracil (5-FU)
  • Capecitabine
  • Oxaliplatin
  • Leucovorin 
Up Next
Chemotherapy for later-stage and metastatic rectal cancer
Chemotherapy for later-stage and metastatic rectal cancer
Stage 3 rectal cancer has spread to nearby lymph nodes. Most stage 3 rectal cancers are treated with chemotherapy, radiation therapy, and surgery.  
Chemotherapy for later-stage and metastatic rectal cancer

Chemo is a treatment for stage 3 rectal cancer that has spread to nearby lymph nodes. You may have it before or after surgery. For rectal cancer that has metastasized (spread) throughout the body, chemo may be the only treatment. 

Treatment for metastatic rectal cancer

Most likely, you’ll have chemotherapy to treat the rectal cancer and the areas it spread to. It can spread to organs that are further away, such as the liver or lungs.  

For cancer that has spread, you may have chemotherapy: 

  • As the only treatment.
  • Before and after surgery.
  • As part of chemoradiation. 
Chemotherapy for later-stage and metastatic rectal cancer

Chemo is a treatment for stage 3 rectal cancer that has spread to nearby lymph nodes. You may have it before or after surgery. For rectal cancer that has metastasized (spread) throughout the body, chemo may be the only treatment. 

Treatment for metastatic rectal cancer

Most likely, you’ll have chemotherapy to treat the rectal cancer and the areas it spread to. It can spread to organs that are further away, such as the liver or lungs.  

For cancer that has spread, you may have chemotherapy: 

  • As the only treatment.
  • Before and after surgery.
  • As part of chemoradiation. 
THE MSK DIFFERENCE

MSK helped pioneer watch-and-wait therapy to treat rectal cancer through long-term monitoring. About half of our patients with rectal cancer avoid surgery to have their rectums removed. People come to MSK to get a second opinion about surgery to remove the rectum. 

Genetic testing for rectal cancer tumors

At MSK, everyone with advanced rectal cancer has their tumor tested using MSK-IMPACT ®. It’s a genetic testing tool only offered at MSK. This testing looks for the most common mutations linked to rectal cancer. 

Genomic testing tells us which mutations may have caused the rectal cancer. This information lets us target those genes for treatment.   

MSK-IMPACT finds genetic changes and other tumor traits that other tests can miss. We routinely test for changes in more than 500 genes. We’ll also look for a genomic condition called microsatellite instability. 

Some standard chemotherapy drugs do not work well on tumors with certain genetic changes. MSK-IMPACT tests for these mutations.  

When we know which mutations caused the rectal cancer, we can choose the best chemotherapy drugs or other treatments. Some chemotherapy works better or worse on tumors that have certain mutations. 

Microsatellite stability or mismatch repair in rectal cancer tumors

We may do genetic testing on the rectal cancer tumor for genetic changes (mutations). We’ll look for mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). These mean there are higher numbers of mutations within each cancer cell.  

About 5 out of every 100 people with metastatic colorectal cancer have MSI-H/dMMR tumors. This also is known as microsatellite instability–high (MSI-H)/deficient mismatch repair (dMMR) metastatic colorectal cancer. 

MSI-H/dMMR makes the tumor less likely to respond to standard chemotherapy. If rectal cancer is dMMR or MSI-H, most people will start with immunotherapy.  

Podcast

How to Manage Side Effects During Cancer Treatment: Fatigue, Hair Loss, Skin Care and More  
Learn ways to prevent or cope with the side effects of chemotherapy and radiation. They can include fatigue (feeling very tired), hair loss, nausea, and skin rashes.  

Listen now

Rectal cancer chemotherapy side effects

Chemotherapy most often works by attacking cells that divide very fast. It can harm cancer cells. But it also can harm healthy cells that divide fast, such as cells that make your hair grow.  

That’s why hair loss can be a side effect of some, but not all, chemotherapy. MSK offers  scalp cooling  as a way to help with hair loss. It involves wearing a cold cap on your head before, during, and after getting chemo. 

Other possible side effects from rectal cancer chemotherapy are:  

  • Fatigue (feeling very tired).
  • Nausea (feeling like throwing up).
  • Vomiting (throwing up).
  • Not wanting to eat.
  • Neuropathy (numbness or tingling in hands and feet).
  • Low blood counts.
  • Chest pain and fever. These are less common. Get treatment right away. 

Some side effects go away soon. Some can be long-term, such as neuropathy.  

We have more information on  managing the side effects of chemo. 

We have ways to help  manage nausea  during chemotherapy.  

Our supportive care team will manage the symptoms and side effects of cancer treatment. 

Rehabilitation medicine doctor Jesuel Padro-Guzman is with his patient at MSK in New York City. 
Chemotherapy-Induced Peripheral Neuropathy (CIPN) may start during chemotherapy or months after treatment ends. 
Rehabilitation medicine doctor Jesuel Padro-Guzman cares for many people with CIPN, a common side effect of chemotherapy. This nerve problem can cause weakness, numbness, pain, and tingling. It’s sometimes called chemo feet and chemo hands. 
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Tools for predicting rectal cancer survival and cancer coming back

MSK’s online prediction tools (nomograms) predict rectal cancer 5-year survival rates and the chance of recurrence after rectal cancer treatment. Our clinical calculators can help your doctor and you make important decisions about treatment and your follow-up care.  

One rectal cancer nomogram predicts whether you’ll have no signs of rectal cancer 5 years after your treatment. It also predicts the chance you’ll survive rectal cancer at least 5 years after treatment. This tool is for people who had chemotherapy, radiotherapy, and surgery for rectal cancer.   

Another rectal cancer nomogram predicts the chance you’ll have no signs of rectal cancer 5 years after your treatment. It’s for people who had total neoadjuvant therapy, which combines chemotherapy and radiation therapy. You must also have had surgery or watch-and-wait active surveillance.  

Learn more about our rectal cancer prediction tools. 

Immunotherapy for rectal cancer

What is immunotherapy? 

Immunotherapy is a form of cancer treatment. It boosts your immune system’s natural ability to fight cancer. Your immune system attacks cancer cells, much the same way it attacks bacteria or viruses. 

Immunotherapy drugs release a brake on the immune system so it can start a stronger attack against cancer.   

We may use these drugs alone or with chemotherapy. Immunotherapy is given through an IV during a visit.  

You may be able to join immunotherapy research studies, also known as clinical trials. Some of these trials may offer early access to promising immunotherapy treatments.   

Immunotherapy may help treat a rare type of rectal cancer caused by mutations in the genes POLE and POLD. 

Which immunotherapy drugs treat rectal cancer?

Immunotherapy drugs to treat rectal cancer include: 

  • Pembrolizumab (Keytruda®)
  • Nivolumab (Opdivo®)
  • Dostarlimab (Jemperli®)
  • Ipilimumab (Yervoy®) 

MSK led research for a new approach to immunotherapy for rectal cancer. It used a drug called dostarlimab. Localized rectal cancer (cancer that has not spread) went away in everyone who took the drug during the research study. The U.S. Food and Drug Administration (FDA) started looking at approving dostarlimab for this use in 2024. 

This treatment is only for rectal tumors with the genetic traits known as  mismatch repair-deficient (MMRd) or microsatellite instability-high (MSI).  Around 5 to 10 out of every 100 people with rectal cancer may have MMRd tumors.

Rectal cancer immunotherapy side effects 

The most common side effects are caused by the immune system having a strong reaction to normal tissues. Side effects often are related to inflammation (swelling) in normal tissues. They can include:  

  • Skin problems, such as a rash or itching. 
  • Chills, fever, fatigue (feeling very tired), and other flu-like symptoms. 
  • Diarrhea (loose poop). 
  • Trouble breathing.
  • Harm to the thyroid gland, treated by pills you must take all your life.
  • Swollen liver or pancreas.
  • Pain from swollen joints.  

We can safely manage most side effects if we treat them early. Sometimes, side effects can harm you. This can happen if they’re not treated right away and affect vital (very important) organs, such as the lungs.  

MSK doctors are experts in caring for people who have side effects from immunotherapy.  

Gastrointestinal medical oncologist Dr. Andrea Cercek stands in an MSK hallway.
The most exciting part of this is that every single one of our patients has only needed immunotherapy. We haven’t radiated anybody, and we haven’t put anybody through surgery.
Medical oncologist Dr. Andrea Cercek co-led MSK research that found immunotherapy worked very well on tumors with a certain genetic makeup.
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Targeted therapy for rectal cancer

Targeted therapies are cancer treatments that target a tumor’s gene changes (mutations or variants). It’s a personal treatment plan just for the type of cancer you have. Targeted therapy medicines most often are given by mouth in pill form or through an IV into your vein.   

You may have a few targeted therapy medicines, or targeted therapy along with chemotherapy.  

Targeted therapies also are called personal medicine, precision medicine, or precision oncology. 

Rectal cancer research is finding more drugs that work by targeting certain proteins in cancer cells. These proteins are made by abnormal (not normal) genes and make rectal cancer cells grow and divide.  

Targeted drugs attack the abnormal proteins in cancer cells. They slow or stop their growth. Most healthy cells are not affected.  

Targeted therapy is used in treating metastatic (stage 4) rectal cancer. Some targeted therapies are being tested in clinical trials for early-stage rectal cancer. 

Video | 1:56 Meet four patients who were successfully treated for rectal cancer thanks to a clinical trial involving immunotherapy at MSK
Hear from the patients about the treatment they received. This approach helps the patients’ own immune systems recognize and attack their tumors, which contain a vulnerable genetic mutation. This treatment allowed the patients to be treated without surgery, radiation, or chemotherapy.

My doctor actually told me that, okay, this is something could possibly change your whole life.

When I originally got the news that I was not going to have to undergo radiation and chemo, I was extremely excited.

Dr. Cercek explained me about the immunotherapy, the benefits.

It went from this really terrifying experience to something where I could feel like, okay, maybe I can get through this.

That day I didn't see the tumor. So, I was thinking, where is the tumor? Then, maybe I thought it's hiding somewhere inside. Doctor told me, there is no more tumor. It's a miracle.

It was like, the world just stopped for a second and I couldn't believe it. You could ask her, I barely reacted because it was just like, I was not expecting to hear that news.

The first thing I did, I called my mom and yeah, we both cried. It was life changing.

I'm not religious at all, but my friends had taken me to a healing mass prior and then I got the news from, I think it was Dr. Cercek that called to say that it was working. So, it was a combination of everybody saying it is miraculous, and then also combined with it actually being miraculous.

You go from feeling, oh, am I going to die? Am I going to lose my colon? And then to find that, oh, you're going to be fine. It's just like, wow. It was an amazing feeling.

If anybody else wants to go through this trial, they might be more comfortable to hear our words.

It definitely saved my life and saved the lives of many others that have been a part of this trial.

I couldn't imagine what my life would be like if this clinical trial hadn't been available

I'm a miracle right here standing without any surgery, don't have cancer. I would say it's not less than a miracle.

 

Watch this video at https://customer-do46zy3q1cub6422.cloudflarestream.com/d462ff04faf347e0b534a028c05c3d84/watch

Genomic testing for targeted therapy

Genomic testing tells us which mutations may have caused the rectal cancer. This information lets us target those genes for treatment.   

Hereditary gene testing tells us if you were born with a gene mutation that raises your chance of getting rectal cancer. Hereditary means genes passed on from parents to children. Mismatch repair deficient/microsatellite instability-high rectal cancers often are hereditary.   

Genomic testing tells us if a tumor has mutated cancer cells. These mutations are not inherited, and they make cancer grow.   

At MSK, genetic testing is a routine part of diagnosis for people who have advanced rectal cancer. This testing can be done on tumor tissue. We also can test your blood samples we collect during a visit. 

Some chemotherapy and immunotherapy drugs work better or worse on tumors that have certain mutations.   

Targeted therapy drugs target: 

  • KRAS
  • BRAF
  • Epidermal growth factor receptor (EGFR) 
  • APC
  • HER2 
  • Vascular endothelial growth factor (VEGF)
  • NTRK
  • RET 

 

Rectal cancer targeted therapy side effects

Targeted therapies in general do not cause hair loss. Targeted therapies also are much less likely to have other  common side effects of chemotherapy, such as low blood counts.  

Common side effects of targeted therapy can include:  

  • Fatigue (feeling very tired).
  • Gastrointestinal (stomach and intestinal) problems. They include nausea (feeling like throwing up) and diarrhea (loose poop).  

Some targeted therapy drugs have other side effects because they target proteins also found in normal cells. 

Your care team will talk with you about what side effects to expect. They have a lot of experience in managing side effects. They offer treatments that can help you feel better. Examples are drugs that help with nausea, and  integrative medicine  treatments.  

Common questions

Common questions about rectal cancer systemic treatments

MSK treats many people with stage 4 metastatic rectal cancer. This is cancer that has spread past the rectum to other parts of the body. 

Our colorectal experts work closely with doctors who treat the liver, lungs, and other areas rectal cancer spreads to.  

Rectal cancer most often spreads to the liver. The blood supply from the large intestine, which includes the rectum, is connected to the liver through a large blood vessel.  

Hepatic arterial infusion (HAI) delivers chemotherapy drugs right to the liver. It uses a tiny pump implanted (put) under the skin in the lower abdomen (belly).  

We use systemic therapies to treat most people with stage 4 rectal cancer. 

MSK has online prediction tools that can help you and your doctor predict rectal cancer 5-year survival rates. They also can calculate the chance of rectal cancer coming back 5 years after treatment.  

These clinical calculators can help your doctor and you make important decisions about treatment and your follow-up care.   

Learn more about our rectal cancer prediction tools.  

Where you get chemotherapy depends on the kind you’re getting, where you live, and other factors. 

You may have your treatment at home, at your doctor’s office, in the hospital, or at one of our MSK regional locations.  

We know your life is busy and it’s stressful to fit chemotherapy sessions into your schedule. We offer chemotherapy at our locations  in: 

  • New York City
  • Long Island
  • Brooklyn
  • Westchester County
  • New Jersey 
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