One recent trend in the development of cancer chemotherapy is a move toward oral administration. Many factors are driving this. Some of these are realistic and practical, while others appear to be less so. Economic considerations are often cited as a reason to pursue development of oral anticancer agents. This implies that overall financial costs of treatment will be lower if parenteral administration can be avoided. Few if any studies, however, have systematically evaluated the financial impact of oral chemotherapy. As such, there are very few data to evaluate, and this discussion of economic considerations is necessarily general and exploratory in nature.
The economic impact of a particular chemotherapy will vary depending upon whether it is viewed from the perspective of the patient, the doctor, the insurer, or the pharmaceutical manufacturer. In attempting to understand these costs, it may be useful to step back and define some terms. When we look at costs, we have to consider the direct medical costs, the direct nonmedical costs, and the indirect costs of an individual therapy (Table 1).
Direct Costs: Direct costs refer to money spent directly on medical care. When we talk about the direct cost of chemotherapy, we are talking about far more than just the cost of the actual drug. There are costs involved in the facilities and equipment used to administer the drugs. We need tubing, we need needles, and we need infusion bags. We need a chair for the patient to sit in and we need a place to put that chair. There are real estate costs for the square footage that is needed for chemotherapy storage, preparation, and administration, whether it is in a doctor’s office or hospital or clinic. Then, there are labor costs (physicians, nurses, technicians, secretaries, support staff, facility maintenance, etc.). There are also nursing costs involved in the follow-up of the patients, and so on. These are the direct costs of chemotherapy. In our current environment, most of these direct costs for chemotherapy are largely borne by third-party payers.
Indirect Costs: Indirect costs of chemotherapy are much more difficult to identify. An example would be the costs incurred because the patient does not have the same earning potential that he or she once did. In addition, their caregivers must expend considerable time and effort in bringing them for chemotherapy treatments and other medical interventions, and so the family caregivers encounter lost wages as well. These costs are absorbed largely by the patient and by society in terms of the lost productivity of the patient. These indirect costs, while potentially quite substantial, are rarely taken into account from the physician or third-party payer’s point of view, yet they may be of paramount importance to the patient.
Nonmedical Direct Costs: Nonmedical direct costs are the costs that the patient directly incurs as a result of the treatment, but are not directly due to the treatment itself. These include the costs of transportation, parking, childcare, and meals while making these trips for treatment, etc. Such costs are directly related to the length and number of office or hospital visits. They are difficult to quantitate, and are largely absorbed by the patient. They also do not figure into most economic analyses, yet from a patient’s point of view, they may be an enormous burden.
For the purposes of this discussion, the direct medical costs of parenteral vs oral treatment will be considered. Drug prices used in this estimation are the currently published average wholesale price (AWP). These may not necessarily reflect actual prices paid, but serve as a useful approximation for comparison purposes.
For parenteral 5-fluorouracil (5-FU), a 5,000-mg vial sells for $28.70. The AWP for leucovorin is $85.75 for 350 mg, which translates to approximately $0.245 per mg. For the purposes of this analysis, let’s look at a hypothetical patient who has a body-surface area of 2 square meters (2.0 m2). Using the Roswell Park schedule of weekly 5-FU at 500 mg/m2 and leucovorin at 500 mg/m2 for 6 weeks followed by a 2-week rest, the drug costs (rounded to the nearest dollar) over an 8-week cycle will be $34 for the fluorouracil(Drug information on fluorouracil) and $1,470 for the leuco-vorin (500 mg/m2 ´ 2.0 m2 ´ $0.245/mg ´ 6 doses = $1,470). (This is assuming a large practice with bulk usage of leucovorin; otherwise, the actual leucovorin cost will be the cost of three vials, or $257 per week, or $1,542 per cycle). Thus, in this hypothetical case, the total chemotherapy cost for 5-FU plus leucovorin works out to $1,504 for the 8-week cycle.
If the leucovorin dose is reduced to 20 mg/m2/week, then the leucovorin dose works out to $10 per dose, or $60 per 8-week cycle. If we choose instead to skip the leucovorin and use a protracted infusion of 300 mg/m2 of 5-FU daily, over the same 8-week period, the drug cost would be $193.
Recall, however, that, as we discussed, the direct costs include more than drugs alone (not to mention that there are other drugs, such as antiemetics, to be considered). The costs of drug administration vary considerably, but the Medicare-allowable drug administration charges can serve as a useful barometer for comparisons. For example, if 5-FU is given by a brief (< 1 hour) infusion, as is typical for lower doses of leucovorin, then the allowable charge is $82.51 (CPT code 96410, chemoinfusion, first hour). If the leucovorin is given over 2 hours, as is done in some centers with the 500 mg/m2 dose, then the charge increases to $144.60 per week, or $867.60 over the 8-week cycle.
Rental charges for ambulatory pumps or cost of disposable ones vary considerably, but usually bring the cost of protracted 5-FU chemotherapy to the range between the high-dose and low-dose leucovorin regimens.
Costs of Oral Fluorinated Pyrimidine Therapy
At the time of this writing, capecitabine(Drug information on capecitabine) (Xeloda) is the only oral fluorinated pyrimidine on the market in the United States, so it is the only one for which we have any actual cost data. The AWP of a 500-mg tablet of capecitabine is $6.40. Using our hypothetical 2.0 m2 patient, and the recommended dose of 2,500 mg/m2/day for 14 days followed by a 7-day rest, the cost of drug for a 3-week cycle would be $64 per day ´ 14 days of treatment = $896. Factoring this out over an 8-week period to permit comparisons with the 5-FU regimens above, the drug cost of 8 weeks of capecitabine would average out to $2,389.
Professional Costs: Professional costs are a bit harder to anticipate, since so many variables are unknown. How often will doctors’ visits be required and how often will nursing interventions be needed? It is clear that oral chemotherapy is complex enough that patients will require considerable education and guidance. This takes professional time, and that costs money. Largely unresolved is the question of how much intervention doctors will think is needed, and what portion of that will third-party payers be willing to reimburse.
If oral agents turn out to require fewer medical office visits and interventions than when parenteral agents are used, then these expenses will drop, but it is far from clear that such a decrease in the need for medical interventions can be expected. More real-world experience with the use of oral fluorinated pyrimidines in clinical practice will be needed to better quantitate the need for doctor and nurse interventions when these oral agents are employed instead of parenteral administration.
Oral vs Parenteral Drugs: Drug costs alone for capecitabine (the only oral fluorinated pyrimidine on the market in the United States at the time of this writing) are higher than for 5-FU. However, some high-dose leucovorin regimens have drug costs that equal or exceed the costs of capecitabine. Administration costs and equipment associated with protracted venous infusion also appear to bring the drug and supply costs to a range comparable to that of the oral agent. A full pharmacoeconomic analysis, however, would have to consider all the other direct medical costs discussed previously. In addition to these direct medical costs, the direct nonmedical costs and the indirect costs, which are very difficult to calculate, would need to be considered. Furthermore, the anticipated cost of follow-up care would need to be assessed, because the various toxicities and other disease-related events would need to be taken into account.
A full outcomes analysis, therefore, would require consideration of all of these economic factors: the full cost of administration, management, value of benefits in terms of productivity, as well as the clinical outcomes and the humanistic outcomes. To make it even more complicated, there is tremendous variability in reimbursement, which makes identification of the final costs very difficult.