Chemotherapy

Lore & Background

Chemotherapy involves the non-specific use of intracellular poisons to inhibit mitosis or induce DNA damage, distinguishing it from more selective hormonal therapies and targeted therapies that block extracellular signals. Traditional chemotherapeutic agents are cytotoxic by interfering with cell division, but cancer cells vary widely in susceptibility. Side effects arise from damage to normal rapidly dividing cells in bone marrow, digestive tract, and hair follicles, leading to myelosuppression, mucositis, and alopecia. Because of its effect on immune cells, chemotherapy is also used for autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.

Reader's Guide

Chemotherapy is a cornerstone of systemic cancer therapy, often combined with local treatments like surgery, radiation, or hyperthermia. Its effectiveness varies by cancer type and stage, ranging from curative for some leukemias to ineffective for certain brain tumors. Dosage is traditionally calculated using body surface area (BSA), a method derived from a 1916 study with only nine subjects, leading to significant pharmacokinetic variability—up to ten-fold differences in drug concentration between individuals.

This variability results in many patients being underdosed or overdosed; for example, a study of metastatic colorectal cancer patients found 68% underdosed and 17% overdosed with 5-fluorouracil when using BSA. Individualized dosing to achieve optimal systemic exposure has been shown to improve treatment response and overall survival while reducing toxic side effects. The legacy of chemotherapy includes its role as a systemic treatment that can reach cancer anywhere in the body, but its limitations in dosing precision and toxicity continue to drive research into more personalized approaches.