Toxicities and adherence in oral biologics

October 9, 2010

Toxicities among oral biologics are numerous and powerful and commonly result in various levels of skin rashes and sores.

“Many of the receptors that are targets of these agents are also present in the skin so it’s not surprising that we would see these skin rashes associated with targeted agents,” said Ethan M. Basch, MD, from Memorial Sloan-Kettering Cancer Center.

Some of the most promising drugs come with side effects including rashes, pustules, calluses, blistering, cracking of the skin on fingers and toes, and ultimately, even permanent skin injury, which can be a life changing complication. One of the toxicities of mTOR inhibitors is painful mouth ulcers. These can be treated with a mild mouthwash (saltwater and baking soda), Dr. Basch said.

Other managements for rashes and skin reactions on the hands and feet include topical or oral steroids, ointments, wearing comfortable walking shoes and wearing gloves for activities such as golfing. High-potency topical steroids are usually given in the care of dermatologists. Non-dermatoligic toxicities include diarrhea and fatigue, loss of taste, decreased appetite, and mouth sores.

Toxicities can have a major impact on a patient’s quality of life and education for both patients and clinicians on what to expect is crucial, Dr. Basch says. Yet, clinicians seem to underestimate the prevalence of these toxicities, he said. That gap was behind the National Cancer Institute’s initiation of a project called the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events or PRO-CTCAE. Basch was awarded a contract to develop and test the project intended to develop an electronic-based system for patient self-reporting of symptom adverse events (AEs) listed in the CTCAE in an effort to improve the accuracy and precision of grading of this class of AEs. The accurate reporting of AEs in clinical trials is a federal requirement that facilitates evaluation of new therapies.

Adherence is another prominent issue with oral biologics. The medical world, excited by oral biologics’ potential quickly switched to them without all the education and development for education in place, said Barbara Given, PhD, RN, FAAN, associate dean of research at Michigan State University. Consequently there is much confusion and poor adherence among patients.

Many factors are behind this, primarily that regimens are varied and complex in number of pills and the schedule for taking them, Dr. Given said. Patients are often asked to take the drugs with complicated on-and-off schedules and are sometimes asked to take different daily doses. Her research set out to see what factors determined whether patients would adhere to their medications and whether patients benefited from interventions such as automated voice reminders and referrals to a symptom toolkit for self-care. A nurse got involved in the 10-week study only after week four and only when the adherence was under 80%. Participants were primarily females, (69%) with an average age in the low 60s, highly educated, and primarily white.

The study found that those who took continuous medications had good adherence levels, but those who had complicated schedules for taking the drugs had much confusion and sometimes took too many drugs. Further complicating adherence for some on varied schedules was that specialty pharmacies were often delivering the drugs early, such as on a Friday so the patient would have the drugs for the weekend and the patients thought that’s when they should take them.

“We also discovered that specialty pharmacies were doing most of the education and guidance on these drugs, so we need to take a look at specialty pharmacies in our planning for education,” Dr. Given said.

Dr. Given’s study also found that neither symptom severity nor depression was related to adherence. Overall, 33% of participants had some adherence problems at eight weeks. Dr. Given found the automated voice reminders add value for the system effect on the outcomes and provider outcomes as well.

Future research should look at safety issues and simplifying the schedules for these patients, she said.

“About 25% of the drugs in the pipeline are oral agents,” she said. “We have to make it easier for our patients to get the treatments they need.”