As the treatment for cancer improves, patients and physicians challenge the harsh side effects of drugs.

As the treatment for cancer improves, patients and physicians challenge the harsh side effects of drugs.

Cancer patients have traditionally endured severe side effects from potent medications in exchange for extended life. However, there is now doubt among patients and doctors about the necessity of such suffering.

A movement has been sparked to significantly alter the method for testing new cancer medications. The U.S. Food and Drug Administration is encouraging pharmaceutical companies to improve their efforts in determining the minimum effective dosage, even if it means a longer process.

Progress in medical care has resulted in a significant increase in the number of individuals who are able to live with incurable cancer for an extended period of time. Jill Feldman, a 54-year-old resident of Deerfield, Illinois, has been living with lung cancer for 15 years, a feat made possible by these advancements. In contrast, both of her parents passed away from lung cancer within months of being diagnosed.

Unfortunately, the medication she takes for her cancer has side effects such as joint pain, fatigue, and mouth sores, which make it difficult to eat and drink comfortably.

According to Feldman, consuming something too hot can result in burning the mouth, which is a constant sensation for him/her.

With approval from her doctor, she has reduced the dosage. However, she desires for pharmaceutical companies to explore lower dosages earlier in the research phase.

She stated that no person should have to suffer from unnecessary negative consequences of medical treatment.

In contrast to other illnesses, the development of cancer drugs has prioritized the search for the “maximum tolerated dose.”

In order to expedite the testing process for chemotherapy drugs, scientists increase the dosage for a small group of individuals in initial studies to determine the maximum amount that patients can handle. This approach of “more is better” is effective for chemotherapy, but may not apply to newer cancer medications, such as the one Feldman is taking, which have more specific targets and mechanisms of action.

Using chemotherapy to treat cancer is comparable to using a battering ram, as it involves aggressive attacks. However, newer cancer drugs function more like a front door key. They specifically target mutations that promote cancer cell growth or boost the immune system to fight against the disease.

Dr. Lillian Siu, who oversees the development of cancer drugs at the Princess Margaret Cancer Center in Toronto, suggests that a smaller dosage may be sufficient to inhibit the growth of cancer cells. She questions the need for higher dosages if the same results can be achieved with a lower amount.

According to FDA representative Chanapa Tantibanchachai, the FDA is using a program called Project Optimus to encourage drug companies to involve a larger number of patients in initial dose-finding trials. This will help gather more accurate information on the effectiveness of lower doses. The main driving force behind the project is the increasing demand from patients and supporters for cancer medications to be more manageable.

A significant number of recent cancer medications were created using the previous approach. This creates issues when patients miss doses or discontinue usage due to adverse effects. Certain dosage recommendations have been officially reduced after the drugs were authorized. In other cases, dose reduction occurs on an individual basis. A study found that nearly half of patients in advanced stage trials for 28 targeted therapy drugs required a decrease in dosage.

Dr. Patricia LoRusso, head of drug discovery at Yale Cancer Center, explained that they were maximizing the dosage to its limit. However, this resulted in unpleasant side effects, forcing them to pause the treatment to allow for recovery. Unfortunately, this can also give the tumor a chance to progress.

There is a significant difference in the amount of medication absorbed by patients. This can be attributed to variations in liver and kidney function, as well as other individual factors. Lowering the dosage for all patients puts some at risk of receiving inadequate treatment, according to LoRusso.

“The question is: Where can we find the optimal solution?” LoRusso inquired.

Dr. Julie Gralow, chief medical officer of the American Society of Clinical Oncology, is planning a 500-patient study to test whether lower doses of two drugs for breast cancer that has spread.

The study will compare two strategies: Starting treatment at the full dose then lowering the dose for side effects versus starting with a lower dose and increasing dosage if the patient does well.

The majority of concerns about large doses have originated from patients with metastatic breast cancer, such as the Patient Centered Dosing Initiative. This organization has conducted impactful surveys among patients and oncologists.

Lesley Kailani Glenn, a resident of Central Point, Oregon, stated that they will continue receiving treatment indefinitely. They are determined to make the most out of life while constantly receiving treatment.

In the past 11 years, while battling the disease, she has successfully climbed Mount Whitney in California, trekked through the Cinque Terre in Italy, and established a nonprofit organization.

Glenn discovered that cancer drug research tends to lean towards using high doses. As a result, she began collaborating with her doctor to find alternative options. She has now been taking medication at lower doses and sometimes even lower than recommended, in order to manage the side effects. Diarrhea is the main issue for her and she wants to be able to go about her daily activities, such as walking her dog and grocery shopping, without having to worry about sudden bathroom trips.

Glenn expressed his concern about not wanting our quality of life to be taken away.

Under Project Optimus, the FDA is promoting the idea of conducting additional comparisons between dosing methods for drugs. Dr. Alice Shaw, head of early cancer drug development at Novartis, expressed concern that this may cause delays in the development process.

“We will need to have more patience and, of course, this will also result in a longer duration to find, register and provide treatment to these patients,” stated Shaw. He also mentioned that adding an additional six months to a year to the process must be weighed against the pressing need for new cancer medications.

Dr. Timothy Yap, a drug developer at MD Anderson Cancer Center in Houston, emphasizes the importance of accurately dosing medication early on. He believes that this will ultimately result in more successful treatments. According to Dr. Yap, if patients do not adhere to their prescribed medication regimen, the drugs will not be effective.


The Howard Hughes Medical Institute’s Science and Educational Media Group provides assistance to the Associated Press Health and Science Department. The AP is solely responsible for all of its content.