Comparison of Anticancer Drug Toxicities: Paradigm Shift in Adverse Effect Profile

Abstract

The inception of cancer treatment with chemotherapeutics began in the 1940s with nitrogen mustards that were initially employed as weapons in World War II. Since then, treatment options for different malignancies have evolved over the period of last seventy years. Until the late 1990s, all the chemotherapeutic agents were small molecule chemicals with a highly nonspecific and severe toxicity spectrum. With the landmark approval of rituximab in 1997, a new horizon has opened up for numerous therapeutic antibodies in solid and hematological cancers. Although this transition to large molecules improved the survival and quality of life of cancer patients, this has also coincided with the change in adverse effect patterns. Typically, the anticancer agents are fraught with multifarious adverse effects that negatively impact different organs of cancer patients, which ultimately aggravate their sufferings. In contrast to the small molecules, anticancer antibodies are more targeted toward cancer signaling pathways and exhibit fewer side effects than traditional small molecule chemotherapy treatments. Nevertheless, the interference with the immune system triggers serious inflammation- and infection-related adverse effects. The differences in drug disposition and interaction with human basal pathways contribute to this paradigm shift in adverse effect profile. It is critical that healthcare team members gain a thorough insight of the adverse effect differences between the agents discovered during the last twenty-five years and before. In this review, we summarized the general mechanisms and adverse effects of small and large molecule anticancer drugs that would further our understanding on the toxicity patterns of chemotherapeutic regimens.

Keywords: adverse effects; antibody; cytochrome P450; large molecules; small molecules; toxicities.

Figure 1

Classification of major anticancer drugs along with their subclasses. This is a representative classification based on mechanism of action. The red letters indicate the major anticancer drug classes, and the black bold letters represent the corresponding examples of drug subclasses.

Figure 2

General mechanism of action and adverse effects of nonspecific vs. targeted anticancer drugs.

Figure 3

Organ-based adverse effects of anticancer drugs with representative examples.