Advanced Colorectal Cancer with Marwan G. Fakih, MD Case 1 - Episode 3
Marwan G. Fakih, MD:TAS-102 has to be given at a full dose. The investigated dosage of TAS-102 on the RECOURSE clinical trial was 25 mg/m2 twice daily day 1 through day 5 on week 1 and week 2. It is very important to maintain the exact dosage given on that clinical trial. Indeed, there has been retrospective analyses looking at the impact of TAS-102 on neutropenia. It has been shown on two studies at least. One is the RECOURSE trial, which has been evaluated retrospectively, as well as on the expanded access trial of TAS-102. Patients who developed grade 3 neutropenia had a better outlook and a better outcome with TAS-102 than patients who did not develop neutropenia. So, on a first instinct, a physician may think, “Oh, a patient has neutropenia, I need to dose down my drug.” That actually may be potentially counterproductive in this particular instance, since most of the benefits were seen in patients who have grade 3 neutropenia. Therefore, I do not recommend dosing down on TAS-102 in patients who have grade 3 neutropenia. What I would recommend in that setting is supportive care and dose delays as needed to administer the therapy.
The current recommendations for dosing with neutropenia are such that you should not dose reduce within cycle unless the patient has an ANC (absolute neutrophil count) of less than 500, or unless the patient has severe side effects, such as febrile neutropenia. However, dose delay should be until the patient recovers their neutrophil count to above 1500. Therefore, if I’m starting a cycle number 2 and a patient comes to me prior to starting cycle number 2 with an ANC of 1000 or 1100, that is a patient where I would delay the dose. However, if I started treatment and the patient presents to clinic, a CBC has been done, say, on day 7, and the ANC at that point was 900 or 1000, that patient will actually receive the second part of cycle number 1 without a dose delay.
To minimize confusion around the schedule of TAS-102, we try to start treatment on a Monday. This makes it simple for the patient. We tell the patient to be treated or to receive their drugs between Monday and Friday, twice a day, and break on the weekend. And then, they start week number 2 again on a Monday. In addition, we ask the patient to chart down their dosage. We give them a calendar and they note when they receive the drug and how much they have received. We go over the number of pills with them and we chart down how many pills they have to receive. TAS-102 is given in two strengths, 15 mg and 20 mg. Therefore, one has to be very careful in counseling the patients, because it could be a different number of pills of different strength.
We typically tell patients to take TAS-102 in the morning and in the evening as much as possible, around 12 hours apart. However, changes between 1 or 2 hours typically do not have or are not expected to result in a big change.
How do we address a situation where a patient has missed a dose or forgotten a dose? In that particular setting, a patient should not make up for a missed dose. They should continue on the scheduled plan and receive the subsequent doses as planned. The patient should not make up for that dose later on beyond that 5 days on week 1 and beyond the 5 days on week 2.
How do I manage a patient with neutropenia? Obviously, it depends on the intensity of the neutropenia. It also depends on any associated symptomatology. A patient who has febrile neutropenia may have to be admitted to the hospital with initiation of IV antibiotics. However, for a patient who is asymptomatic with neutropenia, what we would have to do in that particular setting is just give a patient a little bit extra time until the patient recovers from his neutropenia. There’s also the possibility of administering a G-CSF (granulocyte colony-stimulating factor), Neupogen, for neutropenia support. We often do consider that particular situation where we have either profound neutropenia, such as grade 4 neutropenia with treatment, or where we have experienced a significant delay in re-initiation of cycle number 2. In that particular setting, we typically give patients Neulasta after completion of their first 2 weeks of therapy to allow the bone marrow to recover more quickly. But, that’s an individualized practice.
Case Scenario 1: