What Are the Least Toxic Chemotherapies?

To most people today, chemotherapy refers to a type of cytotoxic, or cell-killing, a medication used to treat cancer. Originally, however, chemotherapy was a term coined by German chemist Paul Ehrlich, who used it to mean simply the use of chemicals to treat disease. So technically, chemotherapy can include anything from antibiotics or even complementary, natural herbal remedies, since they contain chemicals and are being used to treat disease.

Today, some consider the "targeted cancer therapies" among those with the fewest side effects. However, it is often the case that these ​newer therapies are used in conjunction with standard chemotherapy, not alone. And, although targeted therapy drugs do not affect the body the same way that standard chemotherapy agents do, they can still cause side effects. Cancer cells might have more of a certain receptor or target than healthy cells—which targeted therapies may certainly take advantage of—but healthy cells may still be affected.

 A young woman with cancer holding a coffee mug
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The Magic Bullet

The ideal cancer therapy would be something like a magic bullet, and for most malignancies, the ideal therapy does not yet exist. In the late 1800s and early 1900s, scientists began to learn about bacteria and the infectious causes of disease. Paul Ehrlich was a doctor who worked with bacteria, and he believed that, since he could stain bacteria and see them under the microscope, he should also be able to attack these germs if he could find a chemical that would attach itself to the germ and kill it, leaving everything else unharmed. He called such chemicals ‘magic bullets.’

Today, we have versions of these magic bullets known as antibiotics, but even the mildest of antibiotics may still have side effects—or even worse, may cause a dangerous reaction in some individuals called hypersensitivity. This does not mean giving up on the idea of the magic bullet, however.

Effectiveness Versus Toxicity

Unfortunately, many effective cancer therapies are also associated with significant toxicity. Cancer cells generally arise from normal, healthy cells that have accumulated defects—resulting in uncontrolled growth. They are different enough from normal cells that doctors can use medicines to selectively harm the cancer cells in greater proportion than healthy cells, but some healthy cells are invariably affected; these toxicities are sustained by patients and managed by doctors, in the interest of killing the cancer cells and trying to extend a person’s life.

Sometimes there is a direct relationship between increasing anti-cancer effectiveness and increasing toxicity. On the other hand, scientists who analyze the results of clinical trials are always on the look-out for points at which increasing the dose of a drug produces no gains but is associated with greater toxicity. Often times, it is a balancing act that doctors and patients do together—aiming for the best effectiveness with the level of toxicity that is acceptable, in order to realize long-term gains.

Elderly Patients

Although it may be shocking to many, some cancer trials use the age of 60-65 years as a threshold for "elderly" patients. Clearly, the word elderly can be a subjective term as some individuals in their 80s and 90s are in better health than many people who are decades younger. As we age, however, we do tend to develop more chronic health conditions, like high blood pressure. And our kidneys are often not as efficient at filtering our blood as they once were. For these reasons, and for a variety of other factors, our ability to tolerate strong chemotherapy, on average, is not as good at 85 years of age as it might have been at age 20.

Diffuse large B-cell lymphoma (DLBCL), and other types of cancer can be quite common in people who are advanced in years. Indeed, the number of people aged 80 years or older with aggressive B-cell non-Hodgkin lymphoma (B-NHL) has increased in the clinical setting. Treatment regimens for DLBCL in younger people are relatively standardized or settled, at least for the present moment. Efforts to optimize the balancing act between effectiveness and toxicity are now underway for older individuals, too.

Less Toxicity

A group of scientists well known in the world of lymphoma research – the Groupe d'Etude des Lymphomes de l'Adulte (GELA) – examined this question in people with DLBCL ages 80 to 95. They aimed to investigate the efficacy and safety of a decreased dose of CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisone) chemotherapy with a conventional dose of rituximab—a monoclonal antibody targeting cells with the CD20 'tag'—in elderly patients with DLBCL.

So far, at two years out, results have been encouraging, also highlighting the importance of individual patient factors in this age group. When a lower dose chemotherapy regimen, or R-"miniCHOP," was used, efficacy appeared to be roughly comparable at 2 years to the standard dose, but with a reduced frequency of chemotherapy-related hospitalization.

Ongoing trials are also examining the question of whether newer immune checkpoint inhibitors and targeted therapies may be combined to reduce toxicity while treating cancer in elderly patients.

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By Tom Iarocci, MD
Tom Iarocci, MD, is a medical writer with clinical and research experience in hematology and oncology.