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One of the more harrowing parts of getting cancer can be the treatments for it — particularly chemotherapy. While chemotherapy (chemo) kills cancerous cells, it also has side effects like extreme nausea, fatigue, hair loss and increased vulnerability to potentially life-threatening infections.
That's why many doctors and patients cheered research published in the June 3, 2018 issue of the New England Journal of Medicine which said that some women in certain stages of a specific type of breast cancer don't actually need chemotherapy as part of their treatment. Previously, these women would have been prescribed the treatment as a "protective" measure. This news had us wondering, how did chemotherapy start and has it changed over time?
Chemo: The Early Years
The earliest chemo was an accidental discovery. Mustard gas had been commonly used for chemical warfare in both World Wars I and II. During World War II, soldiers and other people who were exposed to the chemical were found to have drastically lowered white blood cell counts. This caused researchers to wonder if less toxic varieties of mustard agents could do the same for cancer patients, many of whom experience abnormally high white blood cell counts. Initial research targeting lymphoma patients was published in 1946 to great fanfare, thanks to findings that nitrogen mustard successfully reduced tumor sizes.
The next major breakthrough was the realization that aminopterin (related to the vitamin folic acid) actually blocks DNA replication in children diagnosed with acute leukemia. This discovery led directly to the research and development of drugs that block cancer cells from growing and reproducing.
That finding was critical to the development of chemo as we know it today. Normal living cells are in a constant state of dividing and growing, but cancer cells replicate with reckless abandon, causing them to grow tumors that take up space that should occupied by helpful, healthy cells. The main goal of modern cytotoxic chemotherapy drugs is to stop cancer cells from dividing, spreading and otherwise wreaking havoc. Some drugs actually cause cancer cells to kill themselves, and others go after the food sources (hormones and enzymes) that the cancer cells rely on to grow and thrive.
Types of Chemo Drugs
We've come a long way from those early days of a tiny handful of drugs. Today, "There are about 50 different chemotherapy drugs, that kill cancer cells by attacking their DNA and proteins that are important for cancer cells to grow," explains Dr. Branimir I. Sikic, professor of medicine (oncology) at Stanford University via email.
Here's a list of the main ones:
Alkylating agents: These drugs damage the DNA of cancer cells, hopefully preventing them from reproducing. They are used in the treatment of many cancers because they can be effective throughout the cell cycle.
Antimetabolites: Most commonly used for leukemias, as well as breast, ovarian and intestinal cancers, these drugs shoot to cause damage to the cancerous cells during the phase when they are copying the cell's chromosomes.
Anti-tumor Antibiotics: These attempt to permanently alter cancer cell DNA, so that the cells can't grow or replicate any more.
Topoisomerase inhibitors: Topoisomerase enzymes help separate DNA strands so they can be copied. The inhibitors get in their way to stop that process, and are particularly useful in cancers that affect the lungs, ovaries, GI tract and some leukemias.
Mitotic inhibitors: These are naturally derived compounds, usually from plants. They pack a dual punch by damaging cells throughout their phases, keeping cancer cells from dividing and preventing enzymes from making the proteins necessary for cell reproduction.
The type of chemo regimen a patient is assigned to depends on many factors, like the form of cancer, how far it has spread and so on.
While chemo doses have not changed over the past 50 years or so, there have been other advances to make the medication easier to handle, says Dr. Evelyn Handel, director of the drugs and biologics programs at NCCN in an email interview. "Although the toxicities associated with these medications remain the same, the supportive care medication options we have to treat the toxicities are vastly improved — for example, better antiemetics [drugs that prevent vomiting and nausea], more choices for premedications, antidiarrheals, antihypertensives, etc.," she notes.
Newer Cancer Therapies
She adds that the toxicities for newer therapies like immunotherapy, hormone therapy and targeted therapies are quite different. These therapies (drugs) block or change specific molecules in cancerous cells, so as to make them act more like noncancerous cells. Traditional chemotherapy kills both cancerous and noncancerous cells. The National Cancer Institute points out that some targeted therapies have fewer side effects than traditional chemo; others just have different side effects.
Currently, cancer outcomes vary widely depending on the type and stage of disease. In addition to chemotherapy and other cancer treatments, early detection and a decline in smoking rates have sparked an increase in cancer survivors. The overall cancer death rate in the U.S. fell by 25 percent between 1990 and 2014. Still, certain cancers have actually experienced an uptick, particularly those associated with aging and obesity, as both factors are increasing in America.
