Anticancer Drugs : An overview - Classification, Drugs

Introduction

Table of Contents

Definition– Anticancer drug, also called antineoplastic drug, any drug that is effective in the treatment of malignant, or cancerous, disease.

There are several major classes of anticancer drugs; these include alkylating agents, antimetabolites, natural products, and hormones.

The anticancer drugs either kill cancer cells or modify their growth. However, selectivity of majority of drugs is limited and they are one of the most toxic drugs used in therapy.

Classification :-

Cure or prolonged remission Chemo therapy is the primary treatment modality that can achieve cure or prolonged remission in:

Acute leukemias
Wilms tumour
Ewing’s sarcoma
Retinoblastoma
Rhabdomyosarcoma
Choriocarcinoma
Hodgkin’s disease
Lymphosarcoma
Burkitt’s lymphoma
Testicular teratomas
Seminoma

Palliation – satisfactory results are obtained (shrinkage of evident tumour, alleviation of symptoms) and life is prolonged by chemotherapy in:

Breast cancer
Ovarian carcinoma
Endometrial carcinoma
Myeloma Prostatic carcinoma
Chronic lymphocytic leukemia
Chronic myeloid leukemia
Non-Hodgkin lymphoma
Head and neck cancers
Lung (small cell) cancer
Many other malignant tumours are less sensitive to drugs life may or may not be prolonged by chemotherapy.

Adjuvant chemotherapy Drugs

Adjuvant (meaning “in addition to”) chemotherapy refers to medicines administered after surgery for the treatment of breast cancer.

It is designed to prevent recurrence of the disease, particularly distant recurrence.

Your doctors may recommend chemotherapy if your breast cancer is invasive, has unfavorable prognostic factors.

4. Neoadjuvant chemotherapy

This refers to medicines that are administered before surgery for the treatment of breast cancer.

Your doctors may recommend neoadjuvant chemotherapy due to the size of the tumor, since the drugs may shrink the tumor and give you more surgical options.

Classification of Drugs :-

A. Cytotoxic drugs

Alkylating agents

Mechlorethamine, Cyclophosphamide, Ifosfamide, Chlorambucil, Melphalan Thio TEPA, Busulfan Carmustine (BCNU), Lomustine (CCNU), Dacarbazine (DTIC), Temozolomide, Methylhydrazine, Procarbazine .

Platinum coordination complexes

Cisplatin, Carboplatin, Oxaliplatin

Antimetabolites

Methotrexate (Mtx) ,Pemetrexed,6-Mercaptopurine (6-MP), 6-Thioguanine (6-TG), Azathioprine, Fludarabine, 5-Fluorouracil (5-FU), Capecitabine, Cytarabine (cytosine arabinoside)

Microtubule damaging agents

Vincristine (Oncovin), Vinblastine, Vinorelbine Paclitaxel, Docetaxel Estramustine

Topoisomerase-2 inhibitors

Etoposide

Topoisomerase-1 inhibitors

Topotecan, Irinotecan

Antibiotics

Actinomycin D (Dactinomycin) Doxorubicin, Daunorubicin,

B. Targeted drugs

Imatinib, Nilotinib Gefitinib, Erlotinib Cetuximab Bevacizumab Sunitinib Bortezomib, Rituximab, Trastuzumab.

C. Hormonal drugs

Letrozole, Anastrozole, Exemestane Flutamide, Bicalutamide Finasteride, Dutasteride Nafarelin, Leuprorelin Triptorelin Hydroxyprogesterone acetate, Ethinylestradiol ,Tamoxifen, Toremifene, Fulvestrant etc.

Drugs Knowledge in Detail

ALKYLATING AGENT

An alkylating antineoplastic agent is an alkylating agent used in cancer treatment that attaches an alkyl group (CnH2n+1) to DNA.

The alkyl group is attached to the guanine base of DNA, at the number 7 nitrogen atom of the purine ring.

Since cancer cells, in general, proliferate faster and with less error-correcting than healthy cells, cancer cells are more sensitive to DNA damage-such as being alkylated.

Alkylating agents are used to treat several cancers. However, they are also toxic to normal cells (cytotoxic), particularly cells that divide frequently, such as those in the gastrointestinal tract, bone marrow, testicles and ovaries, which can cause loss of fertility.

Most of the alkylating agents are also carcinogenic. Hyperthermia therapy is especially effective at enhancing the effects of alkylating agents.

Mechlorethamine is used to treat Hodgkin’s lymphoma (Hodgkin’s disease) and certain types of non- Hodgkin’s lymphoma (types of cancer that begin in a type of white blood cells that normally fights infection); mycosis fungoides (a type of cancer of the immune system that first appear as skin rashes)

Cyclophosphamide it works by slowing or stopping the growth of cancer cells in your body. When cyclophosphamide is used to treat nephrotic syndrome, it works by suppressing your body’s immune system.

Ifosfamide is used to treat cancers including testicular cancer and some types of soft tissue and bone sarcoma.

Chlorambucil sold under the brand name LEUKERAN among others, is a chemotherapy medication used to treat chronic lymphocytic leukemia (CLL), Hodgkin lymphoma, and non- Hodgkin lymphoma. For CLL it is a preferred treatment. It is given by mouth. Common side effects include bone marrow suppression.

Melphalan used to treat myeloma, melanoma, sarcoma and ovarian cancer. It may also be used to treat other cancers.

Thio TEPA is a drug used to treat leukaemia, lymphoma and myeloma. It may sometimes be used to treat other cancer. It is given before a stem cell transplant or bone marrow transplant.

Carboplatin is used to treat ovarian cancer. Carboplatin is also used for other types of cancer, including lung, head and neck, endometrial, esophageal, bladder, breast, and cervical, central nervous system or germ cell tumors; osteogenic sarcoma; and as preparation for a stem cell or bone marrow transplant.

Oxaliplatin is used to treat colon or rectal cancer that has spread (metastasized), it is often given in combination with other anticancer drugs (fluorouracil and leucovorin)

ANTIMETABOLITES

An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism.

The presence of antimetabolites chemical that is part of normal metabolism can have toxic effects on cells, such as halting cell growth and cell division, so these compounds are used as chemotherapy for cancer.

Methotrexate was originally developed and continues to be used for chemotherapy, either alone or in combination with other agents. It is effective for the treatment of a number of cancers, including breast, head and neck, leukemia, lymphoma, lung, osteosarcoma, bladder, and trophoblastic neoplasms.

Pemetrexed has become one of the most frequently prescribed chemotherapeutic agents for advanced nonsquamous NSCLC treatment. It is now approved for first line, maintenance and second or third line treatment of nonsquamous NSCLC (non small cell lung cancer) and is generally well tolerated, with few grade 3 and 4 toxicities.

Mercaptopurine is used alone or with other chemotherapy drugs (Anticancer drugs) to treat acute lymphocytic leukemia (ALL; also called acute lymphoblastic leukemia and acute lymphocytic leukemia; a type of cancer that begins in the white blood cells). Mercaptopurine is in a class of medications called purine antagonists.

Thioguanine is used to treat acute myeloid leukemia (AML; a type of cancer that begins in the white blood cells). Thioguanine is in a class of medications known as purine analogs.

It works by slowing or stopping the growth of cancer cells in your body.

Azathioprine to skin cancers. These are Anticancer drugs used to treat inflammatory bowel disease, arthritis and vasculitis as well as to prevent organ rejection in transplant patients has been identified as an important contributor to skin cancer development.

Fludarabine, sold under the brand name FLUDARA among others, is a chemotherapy medication used in the treatment of leukemia and lymphoma.

These include chronic lymphocytic leukemia, non-Hodgkin’s lymphoma, acute myeloid leukemia, and acute lymphocytic leukemia. It is given by injection into a vein or by mouth.

Capecitabine is used to treat locally advanced breast cancer (also known as regional recurrence) or secondary (metastatic) breast cancer. It’s often given on its own, but can also be given alongside other chemotherapy drugs such as docetaxel.

Cytarabine is used to treat different forms of leukemia, including acute and chronic myelogenous leukemia (AML and CML), acute lymphocytic leukemia (ALL), and acute promyelocytic leukemia (APL).

MICROTUBULE DAMAGING AGENTS

Such as paclitaxel and nocodazole (ND) have been used in the clinical cancer chemotherapy. It is demonstrated that the occurrence of apoptosis or G2/M cell cycle arrest induced by microtubule damaging agents in different cancer cells was through independent mechanisms.

Vincristine is a chemotherapy drug (Anticancer drugs) that belongs to a group of drugs called vinca alkaloids. Vincristine works by stopping the cancer cells from separating into 2 new cells. So, it stops the growth of the cancer.

Vinblastine (VBL), sold under the brand name VELBAN among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin’s lymphoma, non small cell lung cancer, bladder cancer, brain cancer, melanoma, and testicular cancer.

Vinorelbine is a chemotherapy drug used to treat breast cancer. It’s also known by the brand name NAVELBINE.

Paclitaxel used for treatment of breast, ovarian, lung, bladder, prostate, melanoma, esophageal, as well as other types of solid tumor cancers. It has also been used in Kaposi’s sarcoma.

Docetaxel is approved to be used alone or with other anticancer drugs to treat: Breast cancer that is locally advanced or has metastasized (spread to other parts of the body)

Estramustine is a medicine that consists of the combination of two types of drugs – a hormone called estrogen and a chemotherapy drug called nitrogen mustard. It is used for the treatment of patients who suffer from prostate cancer that is no longer responding to hormone treatment.

TOPOISOMER 2 INHIBITOR

Several currently approved chemotherapeutic drugs interfere with the action of topoisomerases.

Currently available topoisomerase inhibitors are irinotecan (CPT-11) and topotecan.

Etoposide is approved to be used with other drugs to treat: Small cell lung cancer. It is used with other chemotherapy as first-line treatment. Testicular cancer.

TOPOISOMER 1 INHIBITOR

Topoisomerase inhibitors block the ligation step of the cell cycle, which generates DNA single- and double strand breaks, leading to apoptotic cell death.

Topoisomerase I inhibitors include irinotecan, topotecan, and camptothecin,

Topoisomerase II inhibitors include etoposide, doxorubicin, and epirubicin.

Topotecan is a chemotherapy drug (Anticancer drugs) which can be used to treat ovarian cancer, small cell lung cancer and cervical cancer.

Irinotecan is a type of drug known by its brand name CAMPTO. It is a treatment for cancer that started in the bowel (bowel cancer). This includes the colon and back passage (rectum).

ANTIBIOTIC

An antibiotic is a chemical made by a microbe that antagonizes the growth of other cells.

Chemotherapy antibiotics are not the same as the ones used to fight bacterial infections. Those drugs disrupt the cell membranes.

Antineoplastic antibiotics bind with DNA, causing these famously coiled molecules to uncoil, thereby preventing RNA synthesis, a key step in protein synthesis.

They also oxidize critical compounds the cells need. In this they are like many chemotherapy medicines.

Antibiotics are used against leukemia, bladder cancer, testicular cancer, and sarcomas.

Dactinomycin, also known as actinomycin D, medication used to treat a cancer like Wilms tumor, rhabdomyosarcoma, Ewing’s sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovarian cancer. It is given by injection into a vein.

Daunorubicin is used with other chemotherapy drugs (Anticancer drugs) to treat a certain type of acute myeloid leukemia (AML; a type of cancer of the white blood cells)and also used with other chemotherapy drugs to treat a certain type of acute lymphocytic leukemia (ALL; a type of cancer of the white blood cells).

Doxorubicin drug called an anthracycline. It slows or stops the growth of cancer cells by blocking an enzyme called topo isomerase 2. Cancer cells need this enzyme to divide and grow.

Epirubicin is used to treat breast cancer. It is used as adjuvant therapy in women who have had surgery and have lymph node involvement. May be used in place of doxorubicin in some circumstances.

Mitoxantrone is used to treat acute myeloid leukaemia (AML), non Hodgkin lymphoma (NHL), breast cancer and primary liver cancer.

Bleomycin is a medication used to treat cancer. This includes Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, testicular cancer, ovarian cancer, and cervical cancer among others. Typically used with other cancer medications, it can be given intravenously, by injection into a muscle or under the skin.

Mitomycin-C used directly into bladder. This substance is designed to stop the cancer cells from growing. Intravesical chemotherapy is used to reduce the frequency of or prevent the tumour(s) from returning.

TARGETED THERAPY

It is a cancer treatment that uses drugs to target specific genes and proteins that are involved in the growth and survival of cancer cells.

Targeted therapy can affect the tissue environment that helps a cancer grow and survive or it can target cells related to cancer growth, like blood vessel cells.

Imatinib a tyrosine kinase inhibitor, was called as “magical bullet,” when it revolutionized the treatment of chronic myeloid leukemia (CML) in 2001.

Nilotinib is used to treat certain type of blood cancer (chronic myelogenous leukemia-CML). It works by slowing or stopping the growth of cancer cells.

Gefitinib is used to treat lung cancer. It works by slowing or stopping the growth of cancer cells.

Gefitinib blocks a certain protein (an enzyme called tyrosine kinase).

Erlotinib It works by blocking particular proteins on cancer cells that encourage the cancer to grow.

Erlotinib blocks proteins called epidermal growth factor receptors (EGFR). Cancers that have these receptors are called EGFR positive.

Cetuximab use in combination with radiation therapy for treating squamous cell carcinoma of the head and neck (SCCHN) or as a single agent in patients who have had prior platinum-based therapy.

Hydroxyurea (Hydrea) is used alone or with other medications or radiation therapy to treat a certain type of chronic myelogenous leukemia (CML; a type of cancer of the white blood cells) and certain types of head and neck cancer (including cancer of the mouth, cheek, tongue, throat, tonsils, and sinuses).

Asparaginase prepared from E. coli, was introduced into cancer chemotherapy over 50 years ago and remains an important agent in the therapy of acute lymphocytic leukemia.

Retinoids are relatively new types of anticancer drugs. They have been used alone or in combination to treat a variety of cancers such as skin cancers, cutaneous T-cell lymphoma, acute promyelocytic leukemia, lung cancer, breast cancer, ovarian cancer, bladder cancer, kidney cancer, and head and neck cancers.

Arsenic trioxide also called Trisenox or ATO. It is a treatment for a type of acute myeloid leukaemia called acute promyelocytic leukaemia (APL).

VELCADE (bortezomib) is approved for the treatment of adults with multiple myeloma (a cancer of the plasma cells). VELCADE is also approved for the treatment of adults with mantle cell lymphoma (a cancer of the lymph nodes).

Rituximab is used to treat certain types of cancer (such as non Hodgkin’s lymphoma, chronic lymphocytic leukemia). Some brands of rituximab are also used to treat rheumatoid arthritis and can decrease joint pain and swelling.

HORMONE THERAPY

Hormone therapy is used to treat cancer that use hormones to grow, such as some prostate and breast cancer.

It is a cancer treatment that slows or stops the growth of cancer that uses hormones to grow.

Also, it is called hormonal therapy, hormone treatment, or endocrine therapy.

Dutasteride is the dual 5a-reductase inhibitor, reduced the incidence of prostate cancer detected on biopsy among men who had an increased risk of prostate cancer.

Nafarelin is equivalent to diethylstilbestrol (stilboestrol) in terms of disease-free survival in men with prostate cancer.

As a reliable method of contraception, nafarelin gives unpredictable results in men and the promising results in women may be offset by hypoestrogenic side effects.

Lupron is a type of hormone therapy for prostate cancer. It works by lowering the amount of testosterone in a person’s body, which helps slow the growth of cancer cells.

Letrozole is used treat early breast cancer in women who have experienced menopause (change of life; end of monthly menstrual periods) and who have had other treatments, such as radiation or surgery to remove the tumor.

Arimidex is an aromatase inhibitor to treat: postmenopausal women diagnosed with hormone-receptor-positive, early stage breast cancer after surgery (or possibly chemotherapy and radiation) to reduce the risk of the cancer coming back.

Tamoxifen is used to treat breast cancer. It is also used to reduce the chances of breast cancer in high-risk patients. This medication can block the growth of breast cancer. It works by interfering with the effects of estrogen in the breast tissue.

Leuprorelin is approved for the treatment of hormone-dependent diseases, including advanced prostate cancer, endometriosis, breast cancer and precocious puberty.

Exemestane is used to treat early breast cancer in women who have experienced menopause (change of life; end of monthly menstrual periods) and who have already been treated with a medication called tamoxifen (Nolvadex) for 2 to 3 years.