Standardization of the body surface area (BSA) formula to calculate the dose of anticancer agents in Japan

Abstract

Background: The importance of deciding the appropriate dose of anticancer agents cannot be overemphasized. Body surface area (BSA) has been used to calculate the dose in anticancer therapy since the 1950s. Japanese oncologists, often use their own Japanese BSA formula instead of western BSA formulae. However, it is not widely known that some discrepancies exist between the BSA products of the Japanese and western styles. On the other hand, recently dose-calculations according to BSA were criticized from the standpoint of pharmacokinetics (PK). Lately, we have had many opportunities for international collaborations, which make it necessary to review these BSA formulae, and the BSA-based dosing method. A unified BSA formula in cancer therapy is needed in Japan.

Methods: We searched and compiled frequently used BSA formulae across the world using the MEDLINE search, oncology text, a web search on cancer clinical trial groups, and personally communicated with medical oncologists from western countries. Using these formulae, we calculated BSA for a typical Japanese individual, and compared their products. We calculated BSA using these formulae for individuals of widely varying physique, from 140 to 185 cm in height, and from 30 to 96 kg in weight, and estimated the amount of discrepancies among them.

Results: Among the various BSA formulae used in western countries, the DuBois formula is the standard. In Japan, the Fujimoto formula has been used frequently. The Fujimoto formula was based on a study of 201 Japanese subjects in 1949. For the average Japanese individual, the BSA calculated using the Fujimoto formula was about 3% lower than that which was calculated by western formulae. The BSA calculated for all heights and body weights using the Fujimoto formula, ranged between 0.7 and 4.8% less than those calculated by using the DuBois formula. The other western formulae showed larger discrepancies than the Fujimoto and DuBois formulae.

Conclusion: BSA-based dosing has failed to standardize the variation in PK for most anticancer agents, and individual dosing techniques are currently being investigated. However, until their clinical utilities are confirmed, it is necessary to depend on the BSA-based calculation for determining the dose of most anticancer agents. The DuBois formula, which is the western standard formula, is validated to a greater extent and its accuracy has been confirmed more than others, including the Fujimoto formula. We recommend the use of the DuBois formula instead of the Fujimoto formula in cancer chemotherapy and propose the standardization of this formula in Japan.