Paul Ehrlich originated the term chemotherapy in 1914; Ehrlich is

credited with the idea of a “magic bullet” which would attack a disease

and leave the healthy parts of the body unaffected. The development of

anti-cancer agents has been by trial and error, serendipity or empiricism.

Over a hundred medicines are now employed in cancer treatment; these

agents are classified according to their chemical structure, similarity to

other compounds, derivation, and biochemical mechanism. Therapies

take advantage of the fact that malignant cells have different metabolic

functions from normal cells. Conventional chemotherapy agents

function by inhibiting mitosis (cell reproduction) and inducing apoptosis

(cell death). Engineered anti-cancer agents (designer drugs) such as

monoclonal antibodies, cytokines, gene therapy vectors, antisense. and

peptide molecules have only been developed recently. No medicines

work by affecting the underlying mutations that cause cancer.

We organize chemotherapy drugs by category

Alkylating Agents

Kinase Inhibitors

Vinca Alkaloids
Anthracyclines

Antimetabolites

Aromatase Inhibitors

Topoisomerase Inhibitors

Half of patients who develop cancer get some form of chemotherapy

treatment. Most chemotherapy drugs kill cancer cells outright, or stop

their reproduction and spread by inhibiting metabolic functions of the

cancer cell. These drugs are called cytotoxic. They can also act on healthy

cells (because they also divide) which is the basis for side effects and

unwanted complications of therapy.

Some chemotherapy agents work in specific parts of the cell’s

reproductive cycle. You see agents that are described as inhibiting the S-

Phase or the M-Phase. Others are non-phase specific.

Other drugs are not explicitly cytotoxic, but instead work by disrupting

the ability of the tumor to stay intact. This is the method of action that

most targeted therapies use.

Chemotherapy is an individual treatment plan designed specifically for

each patient in which a drug or group of drugs is administered by oral or

intravenous injection (or other less commonly used routes such as

intrathecal injection) at a precise dose, based on patient weight, and

given over a finite and defined time period. Adjuvant therapy is

chemotherapy given to high risk patients after other definitive local

therapy (radiation or surgery) has removed the tumor. It is established

therapy for breast, colorectal, osteosarcoma, Wilm’s tumor and some

stages of gastric, non-small lung cell cancers and some melanomas. In

contrast, neoadjuvant therapy is given before other localized therapy

such as surgery or radiation is used. It may be beneficial in treatment of

advanced but limited breast tumors, laryngeal, esophageal, bladder, anal

cancers and some sarcomas.

Growing Industry
A forecast by the management consulting firm McKinsey in 2016 stated

“Oncology is a key driver of growth for the pharmaceutical industry. It is

expected to account for about 30 percent of its product pipeline and 25

percent of pharmaceutical-industry revenue by 2020.”

A large part of this revenue growth is expected to be due to biologics –

first introduced in the 1990s and now a large part of the onoology
treatment arsenal. Other technologies such as cancer vaccines and

antibody delivery systems have the potential to take off.

Alkylating Agents
Alkylating agents were one of the earliest classes of drugs used to treat

cancer, beginning in the 1940’s. Cancer cells are sensitive to DNA

damage. Alkylating agents work by reacting with the proteins that bond

together to form the very delicate double helix structure of a DNA

molecule, adding an alkyl group to some or all of them. This prevents the

proteins from linking up as they should, causing breakage of the DNA

strands and, eventually, the death of the cancer cell. This phenomenon is

essentially a mutation that takes away the cancer cell’s ability to multiply.

While there are many different classes of alkylating agents, they all work

by this same chemical mechanism. Alkylating chemotherapy drugs have

this effect on a cancer cell during every phase of its life cycle, making

them desirable for use on a wide range of cancers. The biggest impact is

on cancers that grow slowly, like solid tumors and leukemia, but they are

also used to treat lung cancer, ovarian cancer, breast cancer, lymphomas,
sarcomas, myelomas, and Hodgkin’s disease. The five major categories

of alkylating agents are nitrogen mustards, nitrosoureas, alkyl sulfonates,

triazines, and ethylenimines.

Nitrogen Mustards
The earliest experiments on human patients date to 1931, and by the

1960s nitrogen mustards were being used to treat leukemia on a fairly

regular basis.

Mechlorethamine, marketed under the trade name Mustargen®, is given

by injection to treat Hodgkin’s disease and non-Hodgkin’s lymphoma,

and as a palliative therapy for breast and lung cancers, and given as a

topical treatment for skin lesions of mycosis fungoides (cutaneous T-cell

lymphoma).

Ifosfamide, sold under the trade name Ifex®, is used to treat both

Hodgkin’s and non-Hodgkin’s lymphoma, as well as recurrent testicular

cancer and germ cell tumors, sarcomas, lung cancer, bladder cancer,

head and neck cancer, and cervical cancer. It is administered

intravenously.
Melphalan is a chemotherapy drug sold under the brand name Alkeran®,

and is also referred to as L-PAM or phenylalanine mustard. It is used to

treat multiple myeloma, ovarian cancer, neuroblastoma,

rhabdomyosarcoma, and breast cancer. It comes as a 2 milligram pill to

be taken daily on an empty stomach. More rarely, it can be administered

by injection.

Chlorambucil is sold by the trade name Leukeran®, and is most widely

used to treat chronic lymphocytic leukemia, malignant lymphomas

including lymphosarcoma, giant follicular lymphoma, and Hodgkin’s

disease. It has also been successfully used to treat non-Hodgkin’s

lymphoma, breast, ovarian and testicular cancer, Waldenstrom’s

macroglobulinemia, thrombocythemia, and choriocarcinoma. It comes

in coated tablet form.

Cyclophosphamide is marketed as Cytoxan® or Neosar®, and is used to

treat Hodgkin’s and non-Hodgkin’s lymphoma, Burkitt’s lymphoma,

chronic lymphocytic leukemia, chronic myelocytic leukemia, acute

myelocytic leukemia, acute lymphocytic leukemia, t-cell lymphoma,

multiple myeloma, neuroblastoma, retinoblastoma, rhabdomyosarcoma,

Ewing’s sarcoma; breast, testicular, endometrial, ovarian, and lung

cancers. Because of the wide variety of cancers it treats, there is also a

wide range of administering options. The most common methods are by

intravenous injection or mouth in the form of tablets. Tablets should be

taken with food and not tampered with. Less commonly, this drug is also

approved to be injected directly into muscle, abdominal lining, or lung

lining.