Cancer therapy is often an excruciating process with numerous debilitating side effects. It is also expensive. Yet, the U.S. Food and Drug Administration (FDA) approves dose and regimens of cancer drugs that are longer – and more costly – than what some experts say is necessary. Northwestern University economist Chuck Manski was placed on monthly infusions of immunotherapy nivolumab for advanced melanoma. The drug severely damaged his thyroid gland and caused severe dryness in his eyes, lips, and mouth. Manski had been on nivolumab for six months, but the FDA-approved protocol was one year. When Manski asked why he needed to endure it for another six months his oncologist could not explain the logic behind the need for further doses. After reading numerous medical journal articles, Manski decided to decline further treatment. The following is what CNN/KFF Health News had to say:
Manski’s decision was in line with what doctors in Canada, Israel, Sweden, and other countries were already doing: giving lower doses of nivolumab, sold under the brand name Opdivo, and of a similar drug, pembrolizumab (Keytruda), or giving them for shorter periods or over longer intervals than the FDA recommended. In India, oncologists found that as little as one-twelfth of the labeled dosage of nivolumab had a powerful impact on several cancers.
Manski joined a group of scholars pushing for additional studies to determine optimal doses of cancer drugs. He and his colleagues believe taking smaller doses for shorter periods could save billions on treatment costs and avoid some of the more severe side effects. Indeed, patients often skip drugs due to cost, undesirable side effects, or mere inconvenience.
A Vanderbilt University study of Medicare enrollees released in 2022 found that 30% of cancer drug prescriptions went unfilled at the pharmacy.
Some experts argue that the needs of patients often take a backseat to drug company profits:
“Decisions aren’t always made with the best needs of the patients in mind. The bottom line is another reason,” said Matthew Goetz, a breast cancer researcher at the Mayo Clinic Comprehensive Cancer Center.
Pharmaceutical companies have shown little interest in dialing back recommended dosages. Once they set the price for a drug, the more sales, the more profit. One study that examined 29 expensive cancer drugs estimated that if minimum necessary dosages had been used in 2024, the U.S. healthcare system could have saved roughly $31 billion.
Pembrolizumab (brand name Keytruda) is FDA approved to treat more than 40 cancers. Nivolumab works in a similar way spurring patient’s immune systems. Both drugs are generally prescribed at a fixed dose, often based on weight. Infusing lower doses would generate less revenue for drugmakers, hospitals and doctors. Some doctors start their patients off at lower doses but there is always a concern that doing so could expose oncologists to lawsuits from patients or their families if the patient dies. Even health insurers sometimes prefer higher doses because manufacturer rebates are based on standard doses.
There have been studies in India, mostly out of necessity, using ultra-low doses of expensive cancer drugs.
…studies in various cancers in which 20- or 40-mg doses of nivolumab biweekly — one-sixth or one-twelfth the recommended dosage — gave Indian patients several months to a year longer survival than patients who underwent chemotherapy, and with fewer side effects.
The data from India offered a glimpse of what could be. However, the studies Patel referred to compared ultralow-dosage immunotherapy to older chemo drugs; none compared ultralow doses against standard nivolumab or pembrolizumab treatments. In India, this would be a sterile exercise, because full-dose treatments are beyond the reach of any but the very wealthy, said Vanita Noronha, an oncologist at Tata Memorial Hospital in Mumbai.
Studies of ultra-low dose immunotherapy drugs like are occurring in India are unlikely to be repeated anywhere else due to ethical concerns. Meanwhile, researchers in Europe are experimenting with lower doses but not ultra-low doses. Some researchers in the United States are experimenting with standard doses for shorter durations.
My late mother developed breast cancer roughly two dozen years ago and chose a nonstandard therapy. Rather than high doses of chemotherapy every three weeks she instead had an ultra-low dose infusions every week. After 18 weeks no traces of cancer remained. Her hair never fell out and the day after the infusion she was merely tired, rather than miserably sick. The evidence suggests that cancer drugs either work or stop working. How well they work and how long they work does not appear to dependent on high doses.
CNN: How much of a cancer drug is too much? Patients, researchers challenge FDA-approved dosages