Indications and Dosing of Methotrexate and 5-FU
Dr. Campen: The interesting thing about methotrexate is that it has been used for such a long time. You would think there would be a specific dose that would be considered “high dose,” but high dose is actually quite variable. [Dosage] depends on the patients and their tolerance of the drug.
Ms. Vogel: I think sometimes we get complacent when dealing with commonly used drugs like 5-FU and methotrexate. Here, we are talking about high-dose methotrexate: the greater the drug dose, the higher the potential for toxicity.
Dr. Schwartzberg: We also should not ignore the possibility of toxicity issues at lower doses. We use [methotrexate] occasionally as a single agent in the palliative setting and as part of combination therapy for breast cancer. Intermediate-dose methotrexate is used in a narrow group of adult cancers. As for 5-FU, we don’t typically think of it in terms of a low dose or a high dose. 5-FU is interesting because its toxicity is based on the way it is delivered and not so much on the dose that is delivered.
Dr. Campen: 5-FU is very much regimen-dependent, especially when it is given in its most common fashion, via continuous infusion. There are many different ways of giving it and many different infusion schedules.
Preventing Malfunction of 5-FU Pumps
Dr. Campen: As a pharmacist, I’m always concerned about pump issues. We require double checks of every pump that goes out for 5-FU and pharmacy calculations. We monitor pharmacy technicians to assure accurate doses of 5-FU are placed into IV bags, check to prevent overfill, and look at prefilled IV tubing for any air. Nurses are also trained in the process and provide patient education about what to do if something goes wrong with the pump. Luckily, we have not had an overdose or pump malfunction that caused an early end to therapy.
Dr. Schwartzberg: I have had pump malfunctions; you cannot be in the business very long without having them. The most common thing that happens is obstruction of the line, so it is more a case of not delivering rather than delivering too much. [Physicians] too instruct patients about their pumps, and when to take out the batteries and call immediately. What are your thoughts on dealing with the residual drug?
Dr. Campen: It is an area of controversy that we too have dealt with in the past at our institution. If a patient comes in early on a 1-day pump, it is much different from a 5-day or 7-day pump. Less than 5% would be a normal amount of bolus delivery, but is there any benefit in doing that? That is the unknown factor. Are you shorting the patient if you stop the infusion early? And sometimes it comes down to toxicity. If the patient has already had a lot of toxicity, giving the remaining drug as a bolus afterward is not in his or her best interest.
Dr. Schwartzberg: [Treatment] definitely needs to be individualized. I am more concerned with the higher dose pumps, when you are doing 1 g/m2 over 4 or 5 days, as opposed to the lower dose in the FOLFOX regimen. Clearly, either one of them can cause problems.
Ms. Vogel: From the nursing side, there is a lot of training involved with educating patients on what to do if something goes wrong with the pump.