Patients with cancer and doctors in the United States are resisting the severe side effects of medications.
Cancer patients have historically endured severe side effects from potent medications in exchange for extended life. However, there is now growing scrutiny from both patients and physicians over the necessity of such suffering.
A movement has been sparked to significantly alter the process of testing new cancer medications, as the U.S. Food and Drug Administration is encouraging drug companies to improve their efforts in finding the minimum effective dosage, even if it means a longer timeline.
Improvements in medical care have allowed countless individuals to live for extended periods of time despite being diagnosed with cancers that cannot be cured. Jill Feldman, a 54-year-old from Deerfield, Illinois, has been able to survive for 15 years with lung cancer due to these advancements. Tragically, her parents both passed away from lung cancer shortly after being diagnosed.
However, her medication for cancer results in discomfort in the joints, exhaustion, and mouth ulcers that cause difficulty with eating and drinking.
Feldman expressed that when consuming a beverage that is too hot, it can result in a painful burning sensation in the mouth. This is a constant discomfort that they experience 24 hours a day.
With approval from her doctor, she has decreased the dosage. However, she believes that pharmaceutical companies should investigate lower doses at the beginning of their research.
She stated that nobody should have to suffer from preventable negative consequences of treatment.
In contrast to other illnesses, the emphasis in cancer medication development has been on determining the “maximum tolerated dose.”
Researchers increase the dosage of chemotherapy drugs in a small group of subjects during initial studies in order to assess the maximum amount of medication that patients can handle. While this approach may be effective for chemotherapy, it may not be applicable to newer cancer drugs, such as the one Feldman is receiving, which are designed to be more precise and have a different mode of action.
Chemotherapy can be compared to a battering ram, using aggressive force as a tactic. However, modern cancer treatments function more like a key to the front door. They focus on specific mutations that drive cancer growth or activate the body’s immune system to aid in the battle against cancer.
According to Dr. Lillian Siu, who oversees cancer drug development at the Princess Margaret Cancer Center in Toronto, a small amount of medication may be sufficient to inhibit the growth of cancer. She questions the rationale for using higher doses when the same result can be achieved with a lower one.
The FDA is utilizing a program known as Project Optimus to encourage pharmaceutical companies to involve a larger number of patients in initial dose-finding trials in order to obtain more accurate information on the effectiveness of lower doses. According to FDA representative Chanapa Tantibanchachai, the project was primarily driven by the increasing demands from patients and advocates for cancer drugs to have more manageable side effects.
Numerous cancer medications were formulated using the traditional approach, which poses challenges when patients miss doses or discontinue taking the medications due to side effects. After approval, some drugs have had their recommended doses officially reduced, while others have had individual patients’ doses lowered. A study found that almost half of patients in advanced trials of 28 targeted therapy drugs required dose reductions.
Dr. Patricia LoRusso, head of drug discovery at Yale Cancer Center, stated that they were increasing the dosage to its maximum limit. However, this often resulted in side effects, leading to a pause in treatment for recovery. This pause gave the tumor an opportunity to continue growing.
There is significant variation among patients. The quantity of medication that enters the bloodstream can differ due to factors such as liver and kidney function and other individual variances. However, this also means that reducing the dosage for all patients could result in underdosing for some, according to LoRusso.
LoRusso stated, “The task at hand is finding the ideal location.”
Dr. Julie Gralow, the head doctor of the American Society of Clinical Oncology, intends to conduct a research study on 500 patients to evaluate the effectiveness of lower doses of two medications for advanced breast cancer.
The experiment will analyze two approaches: initiating treatment at the maximum dosage and then decreasing it for adverse effects, versus beginning with a lower dose and escalating it if the patient responds positively.
A significant portion of the scrutiny towards large doses has been raised by individuals with metastatic breast cancer, including the Patient Centered Dosing Initiative. This organization has conducted impactful surveys involving both patients and cancer physicians.
Lesley Kailani Glenn, a 58-year-old from Central Point, Oregon, stated that they will continue to receive treatment for the remainder of their life. They are determined to make the most of their life, even though treatment will be ongoing.
In the past 11 years, she has accomplished climbing to the top of Mount Whitney in California, trekking the Cinque Terra in Italy, and establishing a charitable organization, all while living with the disease.
After discovering that cancer drug studies prioritize higher doses, Glenn collaborated with her physician. She has been taking medication at lower doses and, if necessary, even lower to cope with the adverse effects. Diarrhea is a major issue for her as she wants to be able to complete daily tasks like walking her dog and grocery shopping without the fear of needing an immediate bathroom trip.
Glenn expressed that he does not want his quality of life to be taken away.
The FDA is promoting increased head-to-head dosing comparisons through Project Optimus. This may potentially impede progress, according to Dr. Alice Shaw, head of early cancer drug development at Novartis.
Shaw stated that the process will need additional patience and time to identify, enroll, and treat patients. This may add six months to a year to the process, which must be carefully considered in light of the pressing demand for new cancer medications.
According to Dr. Timothy Yap, a drug developer at MD Anderson Cancer Center, ensuring correct dosage early on will ultimately result in more successful medications. He emphasizes that if patients do not adhere to the prescribed dosage, the medication will not be effective.