Chemotherapy (chemo) is the specific systematic treatment administered in oncological practice for malignant neoplasms in order to destroy chaotically dividing abnormal cells. Chemo is a part of anticancer treatment along with radiotherapy, immunotherapy and surgery. The drugs used in chemotherapeutic protocols cannot be purchased over the counter; they can be taken with prescription only. Cancer drugs influence and actions are directed to the malignant cell reproduction, cure, control, palliation or chemoprevention.

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Nci-vol-1831-300 Methotrexate.

Image shows open bottle of methotrexate drug—one of the first chemotherapeutic drugs used in the early 1950s


Definition and Background of Chemotherapy Drugs

This type of treatment (chemo) might be used before potentially curative treatment (neoadjuvant). It is used for reducing the size of a tumor prior to surgery as it may be really big.

Hence, radical surgery may cause disfiguration or damage the major organ. Owing to primary therapy, the surgeon would be able to conduct the operation safely, in a less traumatic way (some types of lymphomas, childhood and some adult forms of Hodgkin’s disease, Wilms’ tumor, embryonal rhabdomyosarcoma and small cell lung cancer).

There is a very important disadvantage of the neoadjuvant therapy: If the neoplasm is antitumor-drug-resistant, then the size of the malignant mass would not shrink. Moreover, it would grow intensively and spread metastasis into surrounding tissues and organs with the blood flow and through the lymph system. The ineffectiveness of this method may cost a life, thus, the time matter is a pivotal part of the anticancer treatment.

There is another potentially curative treatment, administered for keeping cancer from coming back (adjuvant). This method is directed toward destroying microscopic malignant cells that may remain after a radical surgery (breast cancer, colorectal cancer, osteogenic sarcoma and Wilms’ tumor).

Also, there is complex treatment conducted together with other methods of anticancer cure (chemoradiation). Due to the fact that a single drug cannot treat cancer, a combination of drugs is usually administered for different types of malignant neoplasms.

Antitumor drugs intake routes:

  • Oral (by mouth)
  • Intramuscular or subcutaneous (injection)
  • Intravenous (IV)
  • Intra-arterial (into the arteries)
  • Intralesional (into the tumor)
  • Intraperitoneal (into the peritoneal cavity)
  • Intrathecal (into the spinal fluid)
  • Topically (applied to the skin)

Side Effects of Chemotherapy Drugs

All of them trigger side effects, such as:

  • Low blood count (most of the anticancer drugs oppress the growth and proliferation of all cells of the body).
  • Alopecia as an after-effect of the radiotherapy.
  • Nausea, vomiting and diarrhea are the signs and companions of the chemo intoxication.
  • Poor appetite as a symptom of severe intoxication.
  • Skin rash, mouth sores, photosensitivity of the skin are the symptoms reflecting the grade of toxicity of the chemo.
  • Infertility occurs in most of the cases for both men and women. That is why those who can afford to keep their semen or eggs in the special banks until their complete recovery, are able to conceive and bear a baby later in their lives.
  • Elevated liver tests take place due to the high aggressiveness of the chemo agents. Thus, the liver is really exposed to the chemical base of the anticancer drugs and manifests in the lysis of hepatocytes.

Cancer drugs are immune suppressors, thus, cannot be taken together with immune stimulants/vaccination and combined with particular groups of drugs.

Daily dosage is counted according to the weight and height of the patient and stage of the malignant process.

Classification of Chemotherapy Drugs

Chemotherapeutic agents can be subgrouped regarding their mechanism of action, chemical structure and similarity to other drugs:

  • Antimetabolites (cell-cycle–specific agents that affect DNA synthesis)
  • Plant Alkaloids
  • Topoisomerase Inhibitors
  • Antitumor Antibiotics
  • Alkylating Agents
  • Nitrosoureas
  • Steroids

Antimetabolites

This group of cancer drugs is administered in order to substitute affected DNA and RNA blocks to normal building blocks of DNA and RNA, on the stage of replication of the chains.

MTX (Methotrexate, common brands: Trexall, Rasuvo)

Table: “Methotrexate.” by Wikipedia:

Pharmacokinetic data
Bioavailability 60 % at lower doses, less at higher doses
Protein Binding 35—50 % (parent drug), 91—93 % (7-hydroxymethotrexate)
Metabolism Hepatic and intracellular
Biological half-life 3—10 hours (lower doses), 8—15 hours (higher doses)
Excretion Urine (80—100 %), feces (small amounts)
Chemical and physical data
Formula C20H22N8O5
Molar Mass 454.44 g/mol
methotrexate

Image: “Methotrexate (green) complexed into the active site of DHFR (blue).” by Fdardel. License: CC BY-SA 3.0

MTX is an “antineoplastic” or “cytotoxic” anti-cancer drug, regarded as antimetabolite, which interferes with DNA synthesis of the cells.

MTX is prescribed for these types of malignant tumors:

Ways of administration of MTX:

  • Intravenous infusion
  • Intramuscular
  • Intraventricular or intrathecal infusion

Fluorouracil (5-FU, common brands: Efudex, Carac, Fluoroplex)

Table: “Fluorouracil.” by Wikipedia:

Pharmacokinetic data
Bioavailability 28—100 %
Protein binding 8—12 %
Metabolism Intracellular and hepatic (CYP-mediated)
Biological half-life 16 Minutes
Excretion Renal
Chemical and physical data
Formula C4H3FN2O2
Molar mass 130.077 g/mol
Structure of Fluorouracil

Structure of Fluorouracil

Fluorouracil (5-FU) is the most often used anticancer drug (antimetabolite), which affects DNA synthesis. 5-FU may be administered together with radiotherapy; causes common side effects as any other chemotherapeutic agents.

The types of cancer where 5-FU is prescribed:

Mercaptopurine (6-MP, common brands: Purinethol, Purixan)

Table: “Mercaptopurine.” by Wikipedia:

Pharmacokinetic data
Bioavailability 5—37 %
Metabolism Xanthine oxidase
Biological half-life 60—120 minutes, longer for its active metabolites
Excretion Kidney
Chemical and physical data
Formula C5H4N4S
Molar mass 152.177 g/mol
Ball-and-stick model of mercaptopurin molecule.

Ball-and-stick model of mercaptopurine molecule.

Mercaptopurine (6-MP) is an antimetabolite (“antineoplastic” or “cytotoxic”) administered for the treatment of acute lymphoblastic leukemia (ALL). 6-MP is taken in the form of tablets.

Thioguanine (6TG, common brands: Tabloid) & Cytarabine (Ara-C, common brands: DepoCyt)

Space-filling model of the tioguanine molecule

Space-filling model of the thioguanine molecule

6TG (Thioguanine) is an antimetabolite (“antineoplastic” or “cytotoxic”) chemotherapy drug. Acute myelogenous leukemia (induction, consolidation and maintenance) is an indication for the administration of 6TG. However, in chronic myelogenous leukemia, it is not preferred. 6TG is in the pill form, prescribed according to the anthropological data of the patient.
Table: “Thioguanine.” by Wikipedia:

Pharmacokinetic data
Bioavailability 30 % (range 14—46 %)
Metabolism Intracellular
Biological half-life 80 minutes (range 25—240 minutes)
Chemical and physical data
Formula C5H5N5S
Molar mass 167.193 g/mol
cytarabine_ball-and-stick

Ball-and-stick model of cytarabine molecule.

Ara-C (Cytarabine) is an antimetabolite (“antineoplastic” or “cytotoxic”) cancer drug. This type of chemotherapeutic remedy is successfully used in different types of leukemia:

  • Acute and chronic myelogenous leukemia (AML and CML)
  • Acute lymphocytic leukemia (ALL)
  • Lymphoma
  • Meningeal leukemia and lymphoma, which affects the lining of the brain and spinal cord.

Table: “Cytarabine.” by Wikipedia:

Pharmacokinetic data
Bioavailability 20 % oral
Protein binding 13 %
Metabolism Liver
Biological half-life biphasic: 10 min, 1—3 hours
Excretion Renal
Chemical and physical data
Formula C9H13N3O5
Molar mass 243.217 g/mol

Antitumor Antibiotics

This type of drugs is used in order to stop replication of cancerous DNA inside the affected cells.

Dactinomycin (trade name: Cosmegen)

Image: “Stick model of the Actinomycin D.” by Гонсо. Licence: CC BY-SA 3.0

Image: “Stick model of the Actinomycin D.” by Гонсо. License: CC BY-SA 3.0

Dactinomycin is an antitumor antibiotic (“antineoplastic” or “cytotoxic”). It’s taken in the intravenous form with caution, as it can cause a damage to the surrounding tissue. It may be used for:

Table: “Dactinomycin.” by Wikipedia:

Pharmacokinetic data
Protein binding 5 %
Biological half-life 36 hours
Chemical and physical data
Formula C62H86N12O16
Molar mass 1255.42 g/mol

Doxorubicin (common brands: Doxil, Adriamycin)

Ball-and-stick model of the doxorubicin molecule, an anti-cancer drug. Colour code: Carbon, C: black Hydrogen, H: white Oxygen, O: red Nitrogen, N: blue  

Ball-and-stick model of the doxorubicin molecule, an anti-cancer drug. Color code:   Carbon, C: black |   Hydrogen, H: white |   Oxygen, O: red |   Nitrogen, N: blue

Doxorubicin is an anthracycline antibiotic (“antineoplastic” or “cytotoxic”). This drug is vesicant that requires careful administration; it exists in intravenous form as well.

This cancer drug is widely used in oncology as the list of the diseases it may cure is quite extended:

Table: “Doxorubicin.” by Wikipedia:

Pharmacokinetic data
Bioavailability 5 % (Oral)
Protein binding 75 %
Metabolism Hepatic
Biological half-life Triphasic: 12 minutes, 3 hours, 30 hours, Mean: 1—3 hours
Excretion Urine (5—12 %), feces (40—50 %)
Chemical and physical data
Formula C27H29NO11
Molar mass 543.52 g/mol

Bleomycin (trade name: Blenoxane)

Bleomycin is an antitumor antibiotic (“antineoplastic” or “cytotoxic”), which is taken intravenously and intrapleurally.

Ball-and-stick model of bleomycin molecule.

Ball-and-stick model of the bleomycin molecule.

Bleomycin is indicated for the most aggressive malignant tumors:

Table: “Bleomycin.” by Wikipedia:

Pharmacokinetic data
Bioavailability Webb absorbed
Biological half-life 2 hours
Excretion Renal (60—70 %)
Chemical and physical data
Formula C55H84N17O21S3
Molar mass 1415.551 g/mol

Review Questions

1. What type of leukemia is Mercaptopurine (6-MP) usually administered for?

  1. Acute lymphoblastic leukemia (ALL)
  2. Chronic lymphoblastic leukemia (CLL)
  3. Acute myeloblastic leukemia (AML)
  4. Chronic myeloblastic leukemia
  5. None of above

2. What group of chemotherapeutic agents does MTX (Methotrexate) belong to?

  1. Antitumor antibiotics
  2. Antimetabolites
  3. Plant Alkaloids
  4. Steroids
  5. Topoisomerase Inhibitors

3. Which antitumor antibiotic is frequently used in the most aggressive cancers?

  1. Bleomycin
  2. Doxorubicin
  3. Dactinomycin
  4. Idarubicin
  5. None of above
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