Understanding What Chemorefractory Means

When Chemotherapy Fails

Table of Contents
View All
Table of Contents

Chemorefractory is a term used to describe cancer that does not respond to chemotherapy (chemo) medications.

Cancer can be refractory to chemotherapy immediately or may become refractory during treatment. In other words, a tumor may respond to chemotherapy at the beginning and get smaller, only to stop responding and not change size or even get bigger later.

This article goes over the basics of chemotherapy and why cancer can be chemorefractory. It also discusses steps healthcare providers take to prevent cancer from being unresponsive to this treatment.

Tumor Response to Chemotherapy Treatment - Illustration by Shideh Ghandeharizadeh

Verywell / Shideh Ghandeharizadeh

What Is Chemotherapy?

There are hundreds of different types of chemotherapy. Your cancer care provider (oncologist) will choose chemo drugs based on the type of cancer you have.

The decision also depends on certain reasons why your cancer may become resistant to a chemo drug. Intrinsic drug resistance happens because of existing factors, like the specific genetic mutations involved in your cancer.

Your oncologist will know the reasons for why that may be a concern. They'll also know why extrinsic drug resistance may lead to chemorefraction. For some cancers, they might only choose one chemo drug. Others need to be treated with a combination of chemo drugs as part of cancer care.

Chemotherapy works by killing cells that grow very fast. This includes cancer cells. However, some healthy cells—like those in your mouth and stomach, blood-forming cells, and cells that make hair—also grow fast.

Unfortunately, chemo doesn't discriminate between the two, leading to side effects.

How Chemo Drugs are Administered

Chemotherapy can be given in several ways, depending on the type of cancer you have and other factors about your health.Some of the most common ways to administer chemo are:

  • Through a vein (intravenous infusion, or IV)
  • A shot (injection) in a muscle or fatty tissue
  • In your cerebrospinal fluid during a procedure called a spinal tap (intrathecal chemotherapy)
  • In your abdomen through a catheter or into your chest through a chest tube

Some drugs are given as a tablet or liquid that is taken by mouth (oral), or applied to your skin (topical) as a cream or lotion.

Chemo Response

Response to treatment describes how effective the chemo drugs are at killing cancer cells. Your response to treatment will be measured at different times—usually after you've had two to three cycles of chemo.

Your healthcare providers can check your response to the treatment in different ways, depending on the type of cancer you have. They may want you to have imaging scans to examine the tumor and your organs. You might also need to have blood tests to measure substances called tumor markers.

The tests are repeated, and your healthcare provider will compare the results to see how well the treatment is—or isn't—working. They may need to change drugs.

For example, esophageal cancer is typically first treated with 5-fluorouracil (5-FU) and cisplatin. If it doesn't work, oncologists might try a different drug, like oxaliplatin, which has also been used to treat ovarian and gastric cancers that were refractory to initial chemotherapies.

Describing Chemo Response

Cancer doctors use several terms to talk about how cancer is responding to treatment:

  • Complete response: All cancer goes away
  • Partial response: Cancer has shrunk but is not entirely gone
  • Stable response: Cancer has not shrunk, but it also has not gotten bigger
  • Cancer has progressed: Cancer has grown, and there is more cancer now than before treatment started (in this case, chemo might be stopped and/or changed to a different type)

Why Cancer Is Chemorefractory

There are many reasons why your cancer could be chemorefractory. For example, some cancer cells change their genetic makeup and become resistant to a drug. Other reasons include:

  • Cancer cells pumping the chemo drug out as soon as it gets inside them
  • Cancer cells repairing their own DNA breaks caused by chemo drugs
  • Cancer cells making their membranes thicker so the drugs can't get inside them
  • Cancer cells that may inactivate the chemo drug, so it doesn't work anymore

If your cancer is chemorefractory, know this: There is nothing you did or didn't do that caused your cancer to not respond to treatment.

What If Chemo Doesn't Work?

When chemo drugs don't work, your oncologist may switch drugs or try a different therapy option. For example, an immunotherapy drug may be added to your treatment.However, they may ultimately recommend palliative care. Its focus is on symptom relief and end-of-life planning. That, too, may include chemotherapy that's meant to extend quality of life rather than cure the cancer. It's important to discuss your options openly with your healthcare team and family.

Prevention

To reduce the chances of chemorefractory cancer, oncologists take their time to ensure they are first giving patients the best chemotherapy regimen. But once cancer becomes chemorefractory to one chemo drug or group of chemo drugs, the chances that it will be resistant to other chemo drugs is high.

Oncologists usually give a combination of chemo drugs to overwhelm cancer before it can become resistant—in other words, they try to use their strongest weapons first.

In addition to choosing the chemo drugs that show the best response rate based on research, your oncologist will also consider other factors when choosing your chemo drugs. For example, your overall health and the side effects of chemotherapy are also important factors.

Summary

While a person has chemo, their oncologist will look at how well a treatment works. If the chemo drugs destroy cancer cells and work well, the cancer is chemosensitive. However, if the drugs are not working, the cancer is chemorefractory.

Cancer cells can be chemorefractory right from the start of treatment or become resistant to treatment over time. Your oncologist may recommend using a different chemo drug or chemo in combination with other treatments.

Ultimately, they also may recommend palliative care to extend quality of life but no longer hope to cure cancer.

A Word From Verywell

Researchers are trying to find ways to optimize cancer response rates and make it less likely that cancer will resist chemotherapy. But if you've been told that you have chemorefractory cancer, there may still be options for your care. Be sure to ask questions to have all the information you need to make informed decisions.

12 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. National Institutes of Health, National Cancer Institute. Definition: Chemorefractory.

  2. National Library of Medicine, MedlinePlus. Types of Chemotherapy.

  3. American Cancer Society. How Chemotherapy Drugs Work.

  4. American Cancer Society. How is chemotherapy used to treat cancer?.

  5. American Cancer Society. Getting IV or injectable chemotherapy.

  6. American Cancer Society. Getting oral or topical chemotherapy.

  7. Mitani S, Kadowaki S, Kato K, Masuishi T, Muro K. Combination of Oxaliplatin and 5-Fluorouracil/Leucovorin for Advanced Esophageal Squamous Cell Carcinoma Refractory or Intolerant to Standard Therapies. Case Rep Oncol. 2019 Apr 9;12(1):304-310. doi:10.1159/000499705

  8. National Institutes of Health, National Cancer Institute. Definition of RECIST.

  9. National Cancer Institute. Why Do Cancer Treatments Stop Working?.

  10. Hong L, Lewis WE, Nilsson M, Patel S, Varghese S, Rivera MJ, et al. Limited Benefit from the Addition of Immunotherapy to Chemotherapy in TKI-Refractory EGFR-Mutant Lung Adenocarcinoma. Cancers (Basel). 2022 Jul 17;14(14):3473. doi:10.3390/cancers14143473.

  11. American Cancer Society. If Cancer Treatments Stop Working.

  12. National Library of Medicine, Medline Plus. When your cancer treatment stops working.

Additional Reading

By Colleen Doherty, MD
 Colleen Doherty, MD, is a board-certified internist living with multiple sclerosis.