Encyclopedia of medication guide for patients with colorectal cancer

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In the past two years, with the deepening of research related to targeting and immunotherapy and genotyping, more and more drugs with good effects and fewer side effects have become new options for  individualized treatment and comprehensive treatment of colorectal cancer patients. Treatment strategies have also advanced from third-line or second-line treatment of colorectal cancer to first-line treatment. The overall treatment expectation of colorectal cancer patients has been greatly improved.

  • Colorectal cancer must be genetically tested before use. If you can’t obtain tissue sections, you can choose blood for testing. At this time, you mainly look at the NRAS, KRAS and BRAF genes.
  • The choice of medication for colorectal cancer is usually a combination of multiple drugs and chemotherapy drugs combined with targeted drugs.
  • After the standard treatment of colorectal cancer, there are still many targeted drugs that can be tried. Even if the treatment effect is not as good as the first-line and second-line, it can still bring survival benefits.
  • After the first-line and second-line treatments are resistant, it is recommended to conduct genetic testing again. If MSI-H or NTRK fusion mutations are detected, immunotherapy or larotinib can be selected.

 

So, how should patients with bowel cancer determine the medication plan?

After the diagnosis of colorectal cancer, doctors will recommend that each patient with metastatic colorectal cancer (mCRC) undergo genetic testing to determine the subgroup of the disease, because this information may predict the prognosis of  treatment. The genes that need to be tested are:

MSI, BRAF, KRAS, NRAS, RAS, HER2, NTRK

Related targeted drugs:

MSI (H)-pembrolizumab; nivolumab

BRAF (+)-Dalafenib, Trimetinib; Verofinil

RAS (KRAS- / NRAS-)-cetuximab; panitumumab (anti-EGFR)

HER2 (+)-trastuzumab

NTRK (+)-Larotinib

Anti-angiogenesis targeting drugs

VEGF: bevacizumab, abercept

VEGFR: ramucirumab, rigofinib, fruquintinib

Chemotherapy drugs include:5-fluorouracil, irinotecan, oxaliplatin, calcium folinate, capecitabine, tigeol (S-1), TAS-102 (trifluridine / tipiracil)

Seeing so many kinds of drugs, how to choose and how to combine with the best effect? Vicki will give you a detailed inventory to see what category you belong to, just go and get a seat!

First-line treatment in colorectal cancer

Before taking the medicine, the doctor will definitely look at the results of the genetic test. If the genetic test report shows that there are no mutations in the RAS or BRAF genes, chemotherapy and anti-EGFR targeted drugs are recommended. It is generally recommended that anti-EGFR targeted drugs must be used on the first line, because the effect will be greatly reduced if used in the back line.

If the effect of this treatment is not good, change to a combination of chemotherapy and anti-angiogenesis inhibitors, bevacizumab is commonly used.

If the patient is not suitable for anti-EGFR targeted drugs, then directly use chemotherapy combined with anti-angiogenesis inhibitors.

When none of the above regimens are effective, another chemotherapy regimen and another anti-angiogenesis inhibitor will be replaced.

The chemistry of colorectal cancer usually chooses multi-drug combination. Doctors combine and match according to the actual situation of patients. Commonly used are:

  • FOLFOX (fluorouracil, calcium folinate, oxaliplatin) or FOLFIRI (fluorouracil, calcium folinate, irinotecan), or combined with cetuximab (recommended for patients with wild-type KRAS- / NRAS-BRAF gene)
  • CapeOx (capecitabine, oxaliplatin), FOLFOX or FOLFIRI, or combined with bevacizumab
  • FOLFIRINOX (fluorouracil, calcium folinate, irinotecan, oxaliplatin)

Second-line treatment

In second-line therapy, we have different anti-angiogenesis inhibitors to choose from.

At the first line, we will use bevacizumab combined with chemotherapy. If the treatment is not effective, we can change the chemotherapy regimen and continue to use bevacizumab. Of course, it is also possible to change another targeted drug at the same time as a chemotherapy regimen, to change to abercept, or to ramucirumab.

Third-line and back-line treatment

The choice of first-line and second-line drug options for colorectal cancer is usually some relatively standard chemotherapy drugs and targeted drugs.

Starting from the third-line treatment is a back-line treatment. The back-line treatment plan can use some oral chemotherapeutics that have just come out, including TAS-102, as well as S-1 (tegio), rifafine, or some immunotherapy, such as pembrolizumab (MSI-H).

TAS-102

TAS-102, an oral chemotherapeutic drug, is a combination product of trifluridine (a nucleoside metabolism inhibitor) and tipiracil (a thymidine phosphorylase inhibitor). The medication is very demanding, and every four weeks is a course of treatment. Take the medicine from Monday to Friday in the first week and the second week, stop the medicine on Saturday and Sunday, stop the medicine in the third week and the fourth week, and then start the next cycle. During this period, if the patient does not have a RAS mutation, it can be used in combination with panitumumab. The premise of this regimen is that the patient has not used panitumumab before.

Tigio

S-1 (Teggio) is also an oral chemotherapeutic drug, which belongs to the fluorouracil derivative class. Oral Teggio capsules 80 mg / m2 / day, 2 times a day, once after breakfast and after dinner, even 14 times Days, withdraw medicine for 7 days;

Regafini

Regefini is an oral anti-angiogenesis targeted drug. It is a light pink oval film-coated tablet. Regofenib has a good effect on the treatment of bowel cancer and can significantly prolong the overall survival of patients with bowel cancer. Recommended dose: The recommended dose is 160 mg (4 tablets, each containing 40 mg of rifafenib), once a day, orally on the first 21 days of each course of treatment, and 28 days as a course of treatment.

Immunity therapy

If the patient finds MSI-H through genetic testing, immunotherapy may be considered. You can consider pembrolizumab only if you want to use a single drug. For patients with MSI-H colorectal cancer, pembrolizumab has a 50% chance of shrinking the tumor.

In addition to single-agent immunotherapy, you can also consider combining different immunotherapy, such as the use of Nivolumab (nivolumab) and Ipilimumab (Ipilimumab) combination, the chance of shrinking the tumor is 55%.

Pembrolizumab alone, nivolumab combined with ipilimumab have been approved by the FDA for follow-up treatment of colorectal cancer patients with MSI-H. The data is relatively mature.

Larotinib

Larotinib is a potent, oral, selective tropomyosin kinase inhibitor that acts on TRKB, TRKB, and TRKC kinases. It was approved in November 2018 for up to 17 cancers, including colorectal Cancer, but the fusion mutation of NTRK1 / 2/3 gene needs to be detected, so Larotinib is also an option for subsequent treatment. Adult patients take 100 mg orally twice daily.

The treatment effect of the back-line is usually not as obvious as the first-line and second-line treatment, but it can also prolong the survival period. Therefore, if we can choose different back-line treatment options, different drugs are used in rotation, and life can also be extended.

What should I do if I don’t tolerate chemotherapy?

In addition, the prognostic factors of patients with colorectal cancer must be considered, that is, the conditions that will affect the treatment effect. The main factors are: distant metastasis of cancer cells, the location of the primary tumor, the  characteristic
s of gene mutations, the response and time interval of previous medications, The degree of weakness of the patient will affect the treatment effect and the choice of drug plan.

Especially for patients who are relatively weak and unable to bear the side effects of chemotherapy, how to choose the medication plan?

The general recommendations are as follows:

①Single targeted drug therapy, if there is no RAS gene mutation, you can choose cetuximab or panitumumab

②Anti-angiogenesis inhibitors cannot be used alone, and must be used together with chemotherapy, so you can choose a combination of chemotherapy drugs with small side effects and targeted therapy, such as irinotecan + bevacizumab (or cetuximab)

③Single drug immunotherapy, such as MSI-H, choose pembrolizumab

Key review

  • Colorectal cancer must be genetically tested before use. If you can’t obtain tissue sections, you can choose blood for testing. At this time, you mainly look at the NRAS, KRAS and BRAF genes.
  • The choice of medication for colorectal cancer is usually a combination of multiple drugs and chemotherapy drugs combined with targeted drugs.
  • After the standard treatment of colorectal cancer, there are still many targeted drugs that can be tried. Even if the treatment effect is not as good as the first-line and second-line, it can still bring survival benefits.
  • After the first-line and second-line treatments are resistant, it is recommended to conduct genetic testing again. If MSI-H or NTRK fusion mutations are detected, immunotherapy or larotinib can be selected.

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