Systemic toxicity, severe side effects, and resistance that leads to recurrence and metastasis.
Drugs should heal, not kill.
Whether the negative effects are imminent or slowly manifesting, they matter.
Cytotoxic chemotherapy was developed by modeling mustard gas used in World War I. Given this history, it is not surprising how toxic it is; what is surprising is that it remains the standard of care for many neoplasia even today.
Targeted therapy aims to specifically target molecular pathways. Targeted therapy is always very vulnerable to recurrence. Cancer consists of highly adaptive, mutating cells. The more “targeted” it is, the easier it is for cancer cells to mutate what is being targeted and become resistant to the drug being used.
Immunotherapy. Most immunotherapy drugs still target single receptors or molecules on immune cells or cancer cells and have the problem of low efficacy, some off-target toxicity to stem cells, and a high risk of recurrence.