Many oral therapies for cancer have a high potential for interactions with other drugs and food creating a ‘delicate balancing act’ for health care professionals to negotiate with their patients.
According to pharmacist Gail Rowan, from the Medicines Information Service at Peter MacCallum Cancer Centre, less direct supervision of oral drug administration also contributed to the ‘potential for misadventure’.
Speaking at the Clinical Oncological Society of Australia (COSA) Annual Scientific Meeting in Sydney, Ms Rowan said drug interactions could both compromise a patient’s response to therapy and increase toxicities.
“A lot of the new agents have potentially high interaction profiles based on the way they are metabolised. With breast cancer for example, everolimus is metabolised through the major liver enzyme pathways Cyt3A4 but also through a transporter system called P-glycoprotein.”
“On the surface, any other drug that affects how Cyt3A4 works will potentially interact with everolimus. But what the data shows is you have to have a drug that interacts with both the Cyt3A4 and the P-glycoprotein for it to become a clinically significant interaction.”
She said everolimus can circumvent its normal route of metabolism when given with drugs that only interact with Cyt3A4.
“But when we put it with a drug that we know inhibits both Cyt3A4 and P-glycoprotein then everolimus can’t circumvent that system so we see a clinically significant change in everolimus levels which causes increased toxicity.”
“We see a lot of this in patients with heart failure or other cardiac disease.”
“It’s something that everyone needs to think about and more so now we are using a lot more of these oral agents.”
Trouble at home
Ms Rowan said the fact patients were taking these medications at home also created some complexities.
“Now if we had them in the hospital and we give them an intravenous drug, then we know exactly what is happening and we follow up with them more frequently as they are coming back every two to three weeks for a dose.”
“Often when they’re on oral agents, patients are not being seen as often and we’re not asking as often or following-up with the patients if they have had any problems or interactions.”
She said some patients didn’t like to report side effects in case it was deemed that the drug wasn’t appropriate for them.
“It’s obviously very unlikely but a fear factor for patients. Compliance can be another issue. When they are taking an oral tablet at home, we rely on patients taking the drug or taking it as directed to maximise the effect.”
Ms Rowan said slip-ups were bound to happen with some drugs such as sorafenib taken on an empty stomach and others such as imatinib taken with food to regulate drug absorption.
“It can get complicated and increases confusion for the patient if we have different rules for different drugs.”
She said a breast cancer protocol combining multiple tablets of lepatinib on an empty stomach and capecitabine with food was one such example.
Dose unit packing didn’t always help because it only separated drugs into morning and night.
“We can set up a diary for patients or smartphone reminders to remember their regimen.”
“We’re also trying to moderate for patients by saying, well it’s best taken on an empty stomach but if the patient isn’t tolerating it then we can give it with food but with a smaller dose.”
Ms Rowan said potential drug interactions were everybody’s responsibility.
“Obviously an oncologist needs to consider what drugs the patient is already on for other conditions as other specialists need to consider what drugs patients are on for their cancer.”