Questioning Standard Cancer Dosages
Chuck Manski, a Northwestern University economist, spent six months in 2022 taking nivolumab for advanced melanoma. The treatment ravaged his body. It destroyed his thyroid and left him with severe dryness in his eyes and mouth. FDA protocols demanded a full year of treatment, yet his oncologist could not explain the rationale. She admitted they used the standard duration because the FDA approved it. Manski found no cancer symptoms left in his body and decided to end the treatment early.
He is not alone in his skepticism. Doctors in countries like Canada, Sweden, and Israel have shifted toward lower doses or shorter treatment durations for drugs like nivolumab and pembrolizumab. Researchers in India observed that even one-twelfth of the standard labeled dose provided a significant impact on solid tumors. These clinical observations challenge the status quo in the United States, where high-dose regimens remain the norm despite the physical toll on patients and the massive financial strain on the healthcare system.
The Financial Incentive Barrier
Clinical trials focused on finding the minimum effective dose rarely occur after a drug hits the market. Pharmaceutical companies face little incentive to pursue these studies. A study of 29 expensive cancer drugs showed that the United States could have saved roughly $31 billion in 2024 if minimum necessary dosages were used. Merck sold nearly $32 billion worth of pembrolizumab last year, making it the primary driver of their revenue. Bristol Myers Squibb saw $10 billion in sales from nivolumab. Because profit often scales with the volume of the drug consumed, manufacturers prioritize standard, higher-dose labeling.
Financial structures further entrench this system. Under the federal 340B program, hospitals serving low-income patients buy drugs at a discount and charge insurers a premium. Medicare physicians receive an additional 6% of the average drug price per infusion. Research by Aaron Mitchell of Memorial Sloan Kettering Cancer Center found that revenue from cancer drugs for doctors and hospitals jumped from $9 billion in 2010 to nearly $36 billion by 2024. Half of these profits come from immunotherapy drugs, leading critics to argue that high doses are maintained for economic survival rather than patient health.
Shifting Toward Patient-Centered Care
Some practitioners now bypass standard protocols to protect their patients. Kathy Miller, an oncologist at the Indiana University School of Medicine, starts metastatic breast cancer patients on 400 milligrams of Kisqali rather than the label-recommended 600 milligrams. Insurers often block these prescriptions because rebates are tied to the standard amount. To avoid these fights, Miller prescribes the full dose but instructs patients to skip one pill per cycle. This is a workaround born of necessity.
Efforts to codify better dosing are beginning to take root. The FDA launched Project Optimus in 2021 to encourage companies to conduct precise dose-ranging studies before launching large clinical trials. While the agency cannot legally mandate post-market dose adjustments or set drug prices, it has started incorporating these principles into new approvals. Smaller pilot programs, such as those within the Veterans Health Administration, have successfully reduced costs by adjusting infusion frequencies.
Ultimately, the push for smaller doses is about quality of life. Patient advocates like Kelly Shanahan note that people facing advanced cancer deserve treatments that don't cause unnecessary suffering. As Manski points out, the medical knowledge required to balance efficacy with side effects is a common good. Until major stakeholders prioritize that good over revenue, the burden of finding the right dose remains with the patients themselves.