Take Away Points:

• Many drugs can be given either orally or by IV.
• A drug’s potency or toxicity cannot be judged by knowing its route of administration.
• Both IV and oral therapies carry their own set of advantages and risks.
• Skipping doses of oral medications is a leading cause of developing resistant disease.
• With oral therapies, WE are ultimately responsible for the timely and continued administration of our medications.

Let’s take a step back and review something that seems so basic that we often overlook how it affects our choices about treatment, specifically taking our meds orally versus by infusion.

I’ll start by addressing some myths and by providing some unknown facts about some well-known therapies:

• It is not true that real old school chemotherapy can only be given IV.
• Chlorambucil is a son of mustard gas chemo drug, but it is taken orally.
• Fludarabine, a very common chemo drug used in CLL, was available as a pill until 2008 in the USA and is still available in Canada and elsewhere where some studies show similar or even better efficacy compared to the same drug IV.
• Also there is no truth to the belief that IV therapy packs a bigger punch that oral meds.

This can be a double-edged sword.

Very early dose-finding trials of oral lenalidomide (Revlimid) resulted in the unfortunate deaths of 2 patients due to tumor lysis syndrome. Likewise, early trials of oral ABT-199, now known as venetoclax resulted in two deaths from tumor lysis syndrome.

Tumor lysis syndrome occurs when large numbers of CLL cells are killed rapidly, leading to the release of cell’s contents into the bloodstream. The kidneys and other organs are significantly challenged to cope with the amount of toxic waste produced. In those cases where some deaths occurred during the early trials described above, the patient’s organs were severely damaged which resulted in death. After the deaths, initial treatment doses were lowered and dosage increases were done gradually and included stringent monitoring and supportive care.

For those of us receiving oral treatments for our CLL, we would most likely be at home if a severe reaction occurred and not under the watchful eye of an oncology nurse at the infusion center with an already established IV access to administer potentially lifesaving drugs.

So when choosing a pill over an infusion, we may not be giving up any potency nor are we shedding any risk.

Cost is another factor. The myth of saving money by swallowing rather than infusing our therapy is fast dying.

Today while some oral meds such as prednisone cost pennies, many others may exceed the price of IV therapies. Insurance coverage varies widely from state to state and country to country, but often ironically drugs administered by a medical doctor in an office or infusion center or hospital have much lower co-pays and out of pocket costs for us patients.

So what are the real differences between oral versus IV treatment?

Adverse events can occur with both, but obviously some IV drugs carry a different set of risks such as bruising, infection, and blood clots at the infusion site. Though these are extremely rare and are not usually an issue with the particular drugs we receive, it always a good idea to save our veins.

Pills are certainly much more convenient. Most of the time, when we are established on a safe and stable dose, we can gulp them down in our PJs in the privacy of our home. They are portable and accessible when we travel.

But that convenience carries different concerns. Absorption can be effected by what we eat and what other medications we take. We don’t usually read the package insert on our infusions, but we really should for any oral meds. Some pills’ pharmacokinetics are profoundly impacted by what else we ingest. Moreover, other illnesses or rarely complications of our CLL can interfere with our ability to get adequate doses of meds through the GI track.

Additionally, the meds themselves can cause local gut reactions from minor diarrhea to life threatening colitis.

And this leads me to the last and perhaps most critical difference.

We are responsible for taking our pills. The hematologist’s office will be on the phone with us immediately if we miss an infusion appointment, but they are not monitoring our medicine cabinets.

We are responsible for being adherent and persistent in our pill popping.  And if we look at the track record of the patients with our cousin leukemia, CML, where skipping doses is a leading cause of developing resistance, we cancer patients are not always doing a super job of caring for ourselves.

At the ASCO 2015 Annual Meeting, abstract 7012 reported that patients who missed more than a week of their oral ibrutinib had almost a three times greater risk of progressive disease than those who didn’t miss doses (31% versus 13% respectively). The link to this important research is here. A nice review of the article and some more in-depth technical discussion of this abstract and another on how the drug’s blood levels affect its efficacy by Dr. Jeff Sharman can be found here on his excellent blog. This is not a trivial point as there are many predictable and unpredictable reasons why we might need to hold our oral meds for a week or more, including the need for elective surgery with ibrutinib.

So in summary, while the decision about oral versus IV may be moot for many of us, as we may only have one logical therapeutic choice that is only is available in one form, when we do have a choice, we should make our decision on the particulars of the drugs and our willingness to embrace the responsibility of being our own chemo nurse if we chose the pill.

For those who prefer to watch and listen, here is the home video of me reading an earlier iteration of the script that has been subsequently revised to detail some of the risks of both taking and missing our oral medications.

The artwork in the background is an homage to Albrecht Durer’s The Four Horsemen of the Apocalypse rendered using only carefully applied bleach on black cotton by Will Koffman.

Brian Koffman 5/22/15