Bai Athur Ridwan, S.Farm.

,
FARMAKOTERAPI IV M.Pharm.Sci., Apt

Colon Cancer
 Mampu Menjelaskan defenisi Kanker kolon

Capain Mampu menyebutkan atau menjelaskan faktor risiko

Pembelajaran atau mekanisme terjadinya kanker kolon

Mampu menyebutkan diagnosis, stadium, dan

penatalaksanaan kanker kolon
Intoduction
Cont.
What Is Colorectal Cancer ?
Colorectal cancer is a cancer that starts in the colon or the rectum. These
cancers can also be named colon cancer or rectal cancer, depending on
where they start.

How does colorectal cancer

start ?
• Most colorectal cancers start as a growth on the inner lining of the colon or rectum.
These growths are called polyps.
• A polyp is a projection (growth) of tissue from the inner lining of the colon into the
lumen (hollow center) of the colon.
The 2 main types of polyps are :

1 2
Colorectal Cancer Risk
Factors
Personal Medical History
• Age; 69 years in men and 73 years in women
• Adenomatous Polyps; particularly multiple adenomas
or size 10 mm or more.
• Inflammatory Bowel Disease; ulcerative colitis or
Crohn’s disease
• type 2 diabetes; such as hyperinsulinemia and elevated
levels of free insulin-like growth factor-1 (IGF-1),
promote tumor cell proliferation.
Cont....

Family History and Inherited

Genetic Risk
•Colorectal Cancer or Adenomatous Polyps
•Hereditary Syndromes
•Enzyme Polymorphisms
Cont....

Lifestyle Factors
•Obesity and Physical Inactivity
•Alcohol and Tobacco Use
•Red Meat, Processed Meat,
and Fat
 Mechanism of Colorectal Cancer
• CRC can arise from one or a combination of three different
mechanisms, namely chromosomal instability (CIN), CpG island
methylator phenotype (CIMP) and microsatellite instability (MSI).
 The classical CIN pathway begins with the acquisition of mutations in the
APC, followed by the mutational activation of oncogene KRAS and the
inactivation of the tumor suppressor gene, TP53. Aneuploidy and loss of
heterozygosity (LOH) are the major players in CIN tumors.

 The CIMP pathway is characterized by promoter hypermethylation of

various tumor suppressor genes, most importantly MGMT and MLH1. This
hypermethylation is often associated with BRAF mutation and
microsatellite instability. In addition, the hypermethylation of the MMR
genes may lead to MSI.
 The MSI pathway involves
the inactivation of genetic
alterations in short
repeated sequences.
 DNA mismatch repair
genes that are responsible
for correcting DNA
replication errors. The
important components of
the DNA mismatch repair
system are ATPases
hMSH2, hMSH6, hMSH3,
hMLH1, hPMS2, hPMS1,
and hMLH3.
This mechanism is often
associated with the
CIMP pathway.
Diagnosis
 Signs and Symptoms
Signs :
 Blood in the stool is the most common sign in symptomatic patients.
 Hepatomegaly and jaundice in advanced disease.
 Leg edema as a consequence of lymph node involvement,
thrombophlebitis, fistula formation, weight loss, and pain in the lower back
or radiating down the legs may be indicative of widespread disease.
Symptoms
 Change in bowel habits (generally an increase in frequency) or rectal
bleeding.
 Constipation, depending on the location of the tumor.
 Nausea, vomiting, and abdominal discomfort.
 Fatigue may be present if anemia is severe.
 Screening for Colorectal
Cancer
 Physical exam
 Biopsy removing small pieces of tissue.
 Colonoscopy
Cont.......
 Blood test
• A CBC measured the number of blood cells in a blood sample. It
Complete Blood includes numbers of white blood cells, red blood cells, and
platelets. Cancer and other health problem cause low or high
Count counts.

• Substances in the blood, such as metabolites, electrolytes, fats,

Chemistry profile and proteins. This test gives important information about kidneys,
liver and other organs are working.

CEA • When colon cancer spreads, it can cause high or low levels of
(carsinoembryonic chemical in the blood. One example is a high Carcinoembryonic
antigen level.
antigen) blood test
Cont.......
Imaging test
• CT (computed tomography) takes many pictures of a body part using x-ray.
Cont.......
Imaging test
• PET/CT
Sometimes CT combined with PET (Positron emission
tomography). Three reasons why you have a PET/CT scan:
 To show how big a tumor is if you have metastases.
 To find metastases other than in the liver would exlcude
surgery.
 PET/CT may be an option if you can’t receive contrast dye for
CT or MRI
Cont.......
Imaging test
• MRI ( Magnetic Resonance Imaging)
MRI uses a magnetic field and radio waves to make pictures.
Staging
The American Joint Committee on Cancer and the Union for International Cancer Control
(UICC) jointly recommend the TNM classification system. This classification takes three
aspects of cancer growth: T (tumor size), N (lymph node involvement), and M (presence or
absence of metastases) into account.
 T (tumor size)
Cont.......
 N (lymph node involvement)
Cont.......
 M (presence or absence of metastases)

The T, N, and M scores are combined to assign the cancer a stage. They are
0, 1 (I), 2 (II), 3 (III) or 4 (IV). The stage are explained below.
The stage of colon cancer
Treatment
 Surgery
Cont.......

 Lymphadenoctomy
A Lymphadenoctomy is a surgery that removes lymph nodes. It is
done at the same time as the colectomy. At least 12 lymph nodes
near to the cancer site should be removed for cancer testing. All
nodes that look abnormal should be removed, too.
 Metastasectomy
Not all metastatic disease can be treated with surgery. The methods
of surgery for metastasectomy vary based on where the cancer has
spread.
Cont.......
Adjuvant Therapy for Colon Cancer
• Adjuvant therapy is not indicated for stage I CRC because more than
90% of patients are cured by surgical resection alone.
• Results of adjuvant chemotherapy studies in patients with stage II
disease are conflicting. Despite a lack of consensus among
practitioners, the approach to treatment of high-risk stages II and III
disease is similar.
• Adjuvant chemotherapy is the standard of care for stage III colon
cancer.
Cont.......

Adjuvant Chemotherapy
• Selection of an adjuvant regimen is based on patient-specific factors,
including performance status, comorbid conditions, and patient
preference based on lifestyle factors.
• For more than 40 years, fluorouracil has been the most widely used
chemotherapeutic agent for the adjuvant treatment of colorectal
cancer, both as a single agent and in combination with other agents.
Newer agents such as oxaliplatin and capecitabine have been
incorporated into combination chemotherapy regimens for the
adjuvant treatment of colon cancer.
Cont...
....
Metastatic Disease
 Initial Therapy
Patients with metastatic colorectal cancer (MCRC) are considered
to have resectable, potentially resectable, or unresectable
metastatic disease.
RESECTABLE OR POTENTIALLY RESECTABLE MCRC
Surgical resection of metastases with curative intent is the
primary goal. Five-year overall survival (OS) rates are improved to
20% to 50% with resection. Best candidates are patients with no
significant medical risk factors, fewer than four hepatic lesions,
CEA (carsinoembryonic antigen) less than 200 ng/mL, small
tumor size, lack of extrahepatic tumor, and adequate surgical
margins.
Cont...
....
 UNRESECTABLE METASTATIC DISEASE
Accepted initial chemotherapy regimens consist of oxaliplatin-
containing regimens (FOLFOX, CapOx), irinotecan-containing
regimens (FOLFIRI), oxaliplatin plus irinotecan plus fluorouracil
plus leucovorin (FOLFOXIRI), infusional fluorouracil plus leucovorin
alone, and capecitabine alone.
Cont...
....
Cont...
....
Cont...
....
Cont...
....
Second-Line Therapy
• The selection of second-line chemotherapy is
primarily based on the type of prior therapy
received, as well as the response to prior
treatments, site and extent of disease, and
patient factors and treatment preferences. The
optimal sequence of regimens has not been
established.
References

Hamza, A.H., Aglan, H.A. and Ahmed,
H.H., 2017. Recent Concepts in the
Pathogenesis and Management of
Colorectal Cancer.
Thanks
NCCN Guidelines for Patients Colon
Cancer.
https://www.nccn.org/patients/guideli
nes/colon/index.html.