Recent media coverage continues to highlight the problems of introducing new, costly cancer chemotherapy agents into the NHS. Regulatory bodies in several countries, including the UK, routinely consider evidence of cost-effectiveness when deciding on reimbursement of new therapeutic agents. Evaluation of cost effectiveness as carried out by the NICE technology appraisal process
requires estimating the drug costs for the average patient, which for most chemotherapy drugs involves calculations based on expected BSA values.
The importance of using accurate data and appropriate calculation methods can be illustrated from experience in the UK, where NICE considered the merits of pemetrexed
compared to docetaxel for the treatment of non-small cell lung cancer. In both cases the manufacturers assumed that doses of docetaxel could be calculated on the basis of a mean BSA of 1.7 m2
for all patients (male and female). The costs of pemetrexed were calculated on a similar basis (erlotinib in tablet form does not require dose adjustment according to BSA). On this basis, it appeared that the extra cost of switching to pemetrexed is £3,006 per patient and for erlotinib is £1,865 per patient.
However, the calculations employed a relatively low mean BSA, and did not take into consideration the effects of the distibution of BSA values in the population. The latter may have a significant effect on the final estimate of incremental cost, due mainly to effects on vial usage. Chemotherapy agents are frequently marketed in large vial sizes, leading to a stepwise rather than continuous increase in vials (and hence cost) with increasing BSA. Although vial sharing may help prevent wastage, this is only possible in relatively large centres for more common tumour types, and may be affected by the stability of the agent.
Using the BSA results for lung cancer patients in , and assuming 70% of such patients are male, the combined population mean BSA would be 1.818. A recalculation using this mean BSA and taking into consideration the distribution of BSA values is shown in Appendix S1
. Incremental drug costs per patient would be £3,712 (23% more than originally proposed) for pemetrexed and £1,840 (1% less) for erlotinib. Differences of this order are likely to have important consequences for pharmacy budgets, and may be decisive in reimbursement decisions. Further discussion and examples of the utility of the data provided by this study are provided in Appendix S2
, based on several NICE technology appraisals.
In the absence of reliable estimates of BSA distribution in UK adult patients with cancer, cost-effectiveness evaluations have previously depended on the use of data derived from studies conducted in other countries (). In this study, we provide an estimate for the overall mean BSA for patients receiving chemotherapy at three centres in England and Wales. Additionally, we have analysed the BSA by geographical area, sex and tumour site. The results were consistent between the three geographical areas (North West England, South England and South Wales), and we therefore believe that these values can be extrapolated across the whole of the UK population.
Unsurprisingly BSA varied with both sex and age. Men had a significantly higher BSA value than women (p<0.0005) and for both men and women the BSA declined with age (). However the association between age and BSA was relatively weak (Pearson correlation coefficient of −0.124 and −0.157 for men and women respectively). Notably, the Dorset patients were older on average than those of the other two centres, but this was not reflected in significantly lower BSA values.
This study was designed to allow calculation of the mean BSA for patients with different tumour types. The tumour sites selected reflect those patients commonly treated with chemotherapy (such as breast cancer). On the other hand prostate cancer, which is primarily treated with hormone therapy was not included. This is reflected in the higher proportion of female patients in this study, as breast cancer and prostate cancer are the most common cancers in men and women respectively. We specifically concentrated on larger groups to eliminate the bias from small numbers of patients treated with chemotherapy for other tumour sites. We feel that most of the tumour site groups are large enough to allow generalisation of results although we acknowledge that we had data on comparatively few (155) head and neck cancer patients. Because of this criterion, we have included two tumour sites, breast and ovary, for which the patients are almost all female, which accounts for the higher proportion of female patients in this study.
It is commonly assumed that patients receiving palliative chemotherapy have a lower BSA than those receiving treatment in the neoadjuvant or adjuvant setting, because the more advanced tumours might be associated with significant anorexia and weight loss. We analysed data from two tumour sites (breast and colorectal carcinoma) to investigate this hypothesis. In both cases, there was no statistically significant difference between the mean BSA results, even though palliative chemotherapy included second and third line regimens. This might be due to stringent patient selection for palliative chemotherapy making it less likely that patients with significant weight loss received chemotherapy.
However, small but statistically significant differences were observed between some tumour groups. In particular, women with ovarian cancer had a significantly lower BSA than those with breast cancer and patients with lung cancer had a significantly lower BSA than those with colon cancer. In both cases this is presumably related to the well known association of both ovarian and lung cancer with significant weight loss and anorexia.
A maximum BSA of 2 m2
is commonly used for dose calculations in obese patients. This capping is based in part on small trials which indicate reduced clearance of some chemotherapy agents in obese patients
. However the results of a recent pharmacokinetic study suggest that, for most evaluated drugs, full BSA should be used for dose calculation
. Additionally, recent studies in breast cancer have indicated dose capping may result in underdosing of some patients
. For this reason we have not incorporated dose capping in our BSA calculations. However we have appended the raw BSA data for each tumour group (Appendix S3
), thus allowing recalculation of BSA, taking capping into account. Notably dose capping at a BSA of 2 may have significant cost implications, as patients dosed on the basis of a BSA exceeding 2 would require a further vial. In our study 28% of male patients and 6.6% of female patients had a BSA over 2.00, and would potentially fall into this bracket. Assuming dose banding with 5% tolerance the proportion would be reduced to 14.5% for men and 2.4% for women.
This study provides a reliable estimate for the mean BSA of men and women receiving chemotherapy in the UK (1.91 and 1.71 respectively). While a tumour specific estimate may be more accurate for some tumour types, these differences were relatively small. This information will not only be of value to those calculating the future cost impact of new chemotherapy agents for which the dose is calculated from the BSA, but also to those estimating the cost-effectiveness of new and established agents.