Chemotherapy History - Cancer Compass an Alternate Route

A cancer analogy: “Imagine going downstairs and finding that your basement is covered in mold. You could put on a mask and spray bleach all over everything. That bleach will kill the mold, but it will probably damage your furniture and your storage boxes as well – in just the same way that the chemotherapy would do to your body. In the end the original problem remains; you still have a damp, dark basement, and without any ventilation or sunlight that mold will grow back.” Dr Kelly Turner, author of Radical Remission: Surviving Cancer Against All Odds

The history of chemotherapy

Chemotherapy began as a deadly weapon that was deployed during WWI. In July 1917, British troops based in Ypres, Belgium, reported seeing a shimmering cloud around their feet and a strange peppery smell in the air. Within 24 hours they were itching uncontrollably, had developed horrific blisters and sores, and were coughing up blood. The men had been poisoned by one of the most deadly chemical weapons deployed during the war– mustard gas. In some cases it took up to six weeks for the men to die. Over 10,000 men were killed in this single battle, with many more seriously injured.

Two decades later, with World War II looming on the horizon, researchers with the Allied Forces feared they would have a repeat of the mustard gas attacks and began working on antidotes. Two doctors at Yale University, Louis Goodman and Alfred Gilman, researched the medical records of the poisoned soldiers and noticed that many of them had a surprisingly low number of immune cells (white blood cells). Goodman and Gilman hypothesized that if mustard gas could destroy normal white blood cells, it seemed likely that it could also destroy cancerous cells as well.

Due to war crimes tribunals regarding the use of chemical weapons, all of their testing had to be done in secret with the nitrogen mustard being referred to as “substance X.” They tested the chemical on mice and eventually found a human volunteer with advanced lymphoma. The man was known as J.D. and he had a massive tumor growing on his jaw with more tumors scattered throughout his body. He couldn’t swallow or sleep and his prognosis was dire. With nowhere else to turn J.D agreed to be injected with the nitrogen mustard. In August of 1942, J.D. was given his first injection of substance X and with each treatment it was reported that his condition improved. He could sleep better, he could swallow better and he began to eat food. It was reported that his pain even faded away for a short period of time. But then the lymphoma returned quickly and he passed away, but because J.D. had a short reprieve from his symptoms, the test was considered successful.

A trial of the chemical soon followed at Sloan-Kettering Cancer Center where doctors treated several breast cancer patients, and a second trial took place in 1943 at Yale University and involved 160 patients. There were no survivors from either of these trials, but researchers were excited to report that chemotherapy had the ability to initially shrink the tumors. Unfortunately, chemotherapy cannot differentiate between normal cells and cancerous cells, so they leave a lot of damage in their wake. This is especially true for cells that are fast dividing such as in the bone marrow, lymphatic cells, the lining of the gut, skin cells and hair cells.

Dr Nicholas Gonzalez on the history of chemotherapy
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Side effects of chemotherapy

Circulatory and Immune System

Anemia- occurs when your body doesn’t produce enough red blood cells, making you feel extremely fatigued. Other symptoms of anemia include feeling lightheaded, difficulty thinking, feeling cold, and a general weakness

Neutropenia- chemo can lower your white blood cell count, which results in neutropenia. White blood cells help to fight infection and ward off illness. People with an immune system weakened by chemotherapy must take precautions to avoid exposure to viruses, bacteria, and other germs.

Thrombocytopenia- low platelet count means you’re more likely to bruise and bleed easily. Symptoms include nosebleeds, blood in vomit or stools, and heavier-than-normal menstruation.

Cardiomyopathy- damage to the heart which can affect the heart’s ability to pump blood effectively. Some chemo drugs can also increase the risk of heart attack.

Nervous and Muscular Systems

Chemo brain- the central nervous system controls emotions, thought patterns, and coordination. Chemotherapy drugs may cause problems with memory, or make it difficult to concentrate or think clearly. These symptoms are sometimes referred to “chemo fog,” or “chemo brain.” This mild cognitive impairment may go away following treatment, or it may linger for years. Severe cases can often add to anxiety and stress.

Peripheral Neuropathy- some chemo drugs can cause pain, weakness, numbness, or tingling in the hands and feet. Muscles may feel tired, achy, or shaky. Reflexes and small motor skills may be slowed. It’s not unusual to experience problems with balance and coordination.

Digestive Problems

Mouth sores and dry mouth can make it difficult to chew and swallow. Sores also may form on the tongue, lips, gums, or in the throat. Mouth sores can make you more susceptible to bleeding and infection. Many patients complain of a metallic taste in the mouth, or a yellow or white coating on the tongue. Food may taste unusual or unpleasant.

These powerful drugs can harm cells along the gastrointestinal tract. Nausea is a common symptom, and may result in bouts of vomiting. However, anti-nausea medications given in conjunction with chemotherapy drugs can help alleviate this symptom.

Other digestive issues include loose stools or diarrhea. In some people, hard stools and constipation can be a problem. This may be accompanied by pressure, bloating, and gas. Take care to avoid dehydration by drinking plenty of water throughout the day.

Side effects involving the digestive system can contribute to loss of appetite and feeling full even though you haven’t eaten much. Weight loss and general weakness are common. Despite all this, it’s important to continue eating healthy foods.

Reproductive Issues

Chemotherapy drugs can have an effect on your hormones. In women, hormonal changes can bring on hot flashes, irregular periods, or sudden onset of menopause. They may become temporarily or permanently infertile. Women on chemotherapy may experience dryness of vaginal tissues that can make intercourse uncomfortable or painful. The chance of developing vaginal infections is increased. Chemotherapy drugs given during pregnancy can cause birth defects. In men, some chemo drugs can harm sperm or lower sperm count, and temporary or permanent infertility is possible. Symptoms like fatigue, anxiety, and hormonal fluctuations may interfere with sex drive in both men and women.

Kidneys and Bladder (Excretory System)

The kidneys work hard to excrete the powerful chemotherapy drugs as they move through your body. In the process, some kidney and bladder cells can become irritated or damaged. Symptoms of kidney damage include decreased urination, swelling of the hands and feet (edema), and headache. Symptoms of bladder irritation include a feeling of burning when urinating and increased urinary frequency.

Skeletal System

Chemotherapy drugs cause calcium levels to drop and can contribute to bone loss. This can lead to cancer-related osteoporosis, especially in post-menopausal women and those whose menopause was brought on suddenly due to chemotherapy. According to the National Institutes of Health (NIH), women who have been treated for breast cancer are at increased risk for osteoporosis and bone fracture. This is due to the combination of the drugs and the drop in estrogen levels. Osteoporosis increases the risk of bone fractures and breaks. The most common areas of the body to suffer breaks are the spine and pelvis, hips, and wrists.

Hair and Skin

Many chemotherapy drugs affect the hair follicles and can cause hair loss within a few weeks of the first treatment.

Some patients will also experience skin irritations like dryness, itchiness, and rash. You may develop sensitivity to the sun, making it easier to burn.

Fingernails and toenails may turn brown or yellow, and become ridged or brittle. Nail growth may slow down, and nails may crack or break easily. In severe cases, they can actually separate from the nail bed.

Secondary Cancers

Alkylating agents are chemo drugs that interfere with a cell’s DNA. These drugs can sometimes cause Acute myeloid leukemia (AML) and Myelodysplastic syndrome (MDS). They include:

Mechlorethamine
Chlorambucil
Cyclophosphamide (Cytoxan^®)
Melphalan
Lomustine (CCNU)
Carmustine (BCNU)
Busulfan

The risk increases with higher drug doses, longer treatment time, and higher dose-intensity (more drug given over a short period of time). Studies have shown that leukemia risk begins to rise about 2 years after treatment with alkylating agents, becomes highest after 5 to 10 years, and then declines. Unfortunately, MDS and leukemia that develop after treatment with alkylating agents tend to be hard to treat and have a poor outcome.

Cisplatin and carboplatin are not alkylating agents, but they attack cancer cells in much the same way. These drugs seem to increase the risk of leukemia (mainly AML), too, but the risk is not as great as with the alkylating agents. This leukemia is hard to treat and tends to have a poor outcome, much like the leukemia that is linked to alkylating agents. The risk of leukemia rises as the amount of drugs used gets higher, and the risk of developing leukemia increases even more if radiation has been given along with cisplatin or carboplatin.

Topoisomerase II inhibitors- stop cells from being able to repair DNA. These drugs can also cause leukemia, mainly AML.

How effective is chemotherapy?

Chemotherapy is most effective for Hodgkin’s Lymphoma, testicular cancer, and childhood leukemia. It is ineffective for most solid tumor cancers as is demonstrated in the chart below. According to a study conducted by the Department of Radiation Oncology at Northern Sydney Cancer Center and published in the December 2004 issue of Clinical Oncology, the actual impact of chemotherapy on a 5-year survival in American adults is a paltry 2.1%. (www.ncbi.nlm.nih.gov/pubmed/15630849)